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Tam, Sau-ping. "Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism /". Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17538865.
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譚秀萍 i Sau-ping Tam. "Gene expression of hypothalamic somatostatin, growth hormone releasingfactor, and their pituitary receptors in hypothyroidism". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31213637.
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Dromey, Jasmin Rachel. "Elucidating novel aspects of hypothalamic releasing hormone receptor regulation". University of Western Australia. School of Medicine and Pharmacology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0133.
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[Truncated abstract] G-protein coupled receptors (GPCRs) form one of the largest superfamilies of cell-surface receptors and respond to a vast range of stimuli including light, hormones and neurotransmitters. Although structurally similar, GPCRs are regulated by many diverse proteins, which allow the specific functions of each receptor to be carried out. This thesis focussed on two well-documented GPCRs, the thyrotropin releasing hormone receptor (TRHR) and gonadotrophin-releasing hormone receptor (GnRHR), which control the thyroid and reproductive endocrine pathways respectively. Although each of these anterior pituitary receptors is responsible for distinct physiological responses, both are integral to normal development and homeostasis. This thesis focused on three areas of GPCR regulation: ?-arrestin recruitment, transcription factor regulation and receptor up-regulation. The role of the cytoplasmic protein, ?-arrestin, has perhaps been previously underestimated in GPCR regulation, but it is now increasingly apparent that ?-arrestins not only inhibit further G-protein activation and assist in GPCR internalisation but also act as complex scaffolding platforms to mediate and amplify downstream signalling networks for hours after initial GPCR activation. It is therefore becoming increasingly important to be able to monitor such complexes in live cells over longer time-frames. ... Members of the E2F transcription family have been previously identified by this laboratory as potential GnRHR interacting proteins, via a yeast-2-hybrid screen and BRET. This thesis further investigated the role of E2F family members and demonstrates that a range of GPCRs are able to activate E2F transcriptional activity when stimulated by agonist. However, despite GnRHR displaying robust E2F transcriptional activation upon agonist stimulation, this did not result in any conclusive evidence for functional regulation, although it is possible E2F may modulate and assist in GnRHR trafficking. Furthermore it is apparent that E2F family members are highly redundant, as small effects in GnRHR binding and cell growth were only observed when protein levels of both E2F4 and E2F5 were altered. During the course of the investigation into the effect of E2F transcription on GPCR function, it was evident that long-term agonist stimulation of GnRHR had a profound effect on its expression. As this was explored further, it became clear that this agonist-induced up-regulation was both dose- and time-dependent. Furthermore, altering levels of intracellular calcium and receptor recycling/synthesis could modulate GnRHR up-regulation. In addition, an extremely sensitive CCD camera has been used for the first time to visualise the luciferase activity attributed to GnRHR up-regulation. Overall, this thesis demonstrates the complex nature of GPCR regulation. For the first time, long-term BRET analysis on ?-arrestin interactions with both classes of GPCRs has been examined in a variety of cellular formats. This has given valuable insights into the roles of phosphorylation and internalisation on ?-arrestin interaction. Additionally, this thesis has revealed that prolonged agonist exposure increases receptor expression levels, which has major implications for drug therapy regimes in the treatment of endocrine-related disorders and tumours.
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Ladyman, Sharon Rachel, i n/a. "Characterisation of hypothalamic leptin resistance during pregnancy in the rat". University of Otago. Department of Pharmacology & Toxicology, 2006. http://adt.otago.ac.nz./public/adt-NZDU20070427.154329.
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Leptin is primarily an adipose-derived hormone that acts in the hypothalamus to regulate body fat levels by suppressing appetite and increasing metabolic rate. Pregnancy is characterised by increased food intake and fat mass to meet the metabolic demands of this physiological state. Leptin concentrations also increase during pregnancy, but this does not prevent the pregnancy-induced hyperphagia, suggesting a state of leptin resistance. The aims of this thesis were to measure hypothalamic leptin responsiveness during pregnancy and to investigate the potential mechanisms underlying pregnancy-induced leptin resistance.
The satiety response to intracerebroventricular (i.c.v) leptin was measured in fasted non-pregnant (diestrous), early pregnant (day 7), and mid-pregnant (day 14) rats. Serial blood samples collected from another group of rats demonstrated that despite initial elevated plasma leptin concentrations in pregnant rats, fasting significantly decreased leptin concentrations so that pregnant and non-pregnant groups had similar, low leptin concentrations. Leptin treatment significantly reduced food intake in non-pregnant and early pregnant rats but not in mid-pregnant rats. In addition, there was no post-fasting hyperphagic response in the pregnant rats. These results indicate that pregnant rats become resistant to the satiety action of leptin.
To investigate the mechanisms underlying pregnancy-induced leptin resistance, leptin-induced activation of hypothalamic leptin-target neurons was examined. Signal transducer and activator of transcription 3 (STAT3) phosphorylation was measured in non- pregnant and mid-pregnant rats following i.c.v. administration of leptin. Western blot and immunohistochemistry analysis indicated that leptin-induced STAT3 phosphorylation was significantly reduced in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy. A suppression in the amount of leptin-induced STAT3 activation was observed in the arcuate nucleus during pregnancy, yet there was no overall change in the number of leptin responsive neurons compared to non-pregnant rats. This raises the possibility of a decrease in the degree of responsiveness of arcuate nucleus neurons to leptin during pregnancy. Using double-labelled immuno-histochemistry for alpha-melanocyte stimulating hormone (α-MSH) and leptin-induced pSTAT3 it was demonstrated that pro-opiomelanocortin (POMC) neurons remain responsive to leptin during pregnancy. In the VMH, consistent with the reduced pSTAT3, pregnancy also induced a 2-fold reduction in mRNA for the long form of the leptin receptor (Ob-Rb), the only isoform with full signal transduction capabilities. Expression of mRNA for one of the short forms of the leptin receptor (Ob-Ra) in the choroid plexus was decreased in early and late pregnancy, suggesting that reduced leptin transport into the brain may contribute to pregnancy-induced leptin resistance. CSF/plasma leptin concentration ratios did not differ between pregnant and non-pregnant rats however, suggesting unimpaired leptin transport during pregnancy.
These results indicate that pregnancy is a state of hypothalamic leptin resistance and is associated with impaired activation of the leptin-induced JAK/STAT3 signalling pathway in the VMH and arcuate nucleus, and reduced expression of Ob-Rb mRNA in the VMH. This state of leptin resistance represents an important adaptation of the maternal brain allowing increased food intake and fat mass so that the maternal body can meet the metabolic demands of pregnancy and prepare for the subsequent demands of lactation.
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Innala, Leyla. "Organizational effects of gonadal hormones on the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor responses in male and female rats". Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58874.
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Neonatal gonadal hormones during critical periods of development can irreversibly alter the adult hypothalamic-pituitary-adrenal (HPA) axis. The aims of this thesis were to investigate the role of neonatal gonadal hormones to 1. have direct organizational effects on the HPA axis or via indirect effects on corticosterone binding globulin that lead to compensatory changes in HPA output and 2. if changes in HPA output are met by changes in glucocorticoid receptor (GR) responses. To assesses these questions, the neonatal hormone milieu in Long Evan rats were manipulated in males by blocking the conversion of testosterone to estradiol with an aromatase blocker (ATD) and in females by administering testosterone propionate (TP). As adults, we assessed the influence of neonatal hormone manipulations on plasma corticosterone levels and GR activation in response to acute and repeated restraint exposure. GR responses were assessed using western blots to analyze GR translocation (nuclear/ nuclear and cytoplasm) and phosphorylation of GR at the serine 211 site (Ser211). We then assessed if changes in GR translocation and Ser211 followed restraint induced changes in total and estimated free CORT levels. Our results showed significant differences in corticosterone levels in neonatal ATD treated male and TP treated female rats compared to their same sex control groups under basal-naïve conditions and after restraint exposure, respectively. In both sexes, for GR translocation and Ser211, there was a main effect of restraint stress exposure, and overall significant positive correlations with CORT (total and estimated free) levels. GR translocation was lower in neonatal TP treated females, with no effect in Ser211. Differences between male neonatal ATD and Sham groups were observed compared to untouched controls in Ser211, indicating the effects of the neonatal ATD treatment appear to be due to effects of surgery and gonadal hormone milieu exposure. Adult gonadal hormone levels differed between female neonatal groups, which are likely due to organizational effects of the neonatal treatments. The current study demonstrates neonatal gonadal hormones have long lasting effects on adult corticosterone outputs and sequential GR responses.Medicine, Faculty of
Graduate
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Solomon, Matia B. "The Effect of Gonadal Hormones on Agonistic Behavior in Previously Defeated Female and Male Syrian Hamsters". Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/psych_diss/13.
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Following social defeat, male hamsters exhibit behavioral changes characterized by a breakdown of normal territorial aggression and an increase in submissive/defensive behaviors in the presence of a non-aggressive intruder (NAI). We have termed this phenomenon conditioned defeat (CD). By contrast, only a small subset of defeated females exhibit submissive/defensive behavior in the presence of a NAI. We hypothesized that fluctuations in gonadal hormones might contribute to differences in the display of submissive behavior in intact female hamsters. Following social defeat, proestrous females (higher endogenous estradiol) were more likely to display conditioned defeat compared with diestrous 1 (lower endogenous estradiol) females. This finding suggests that there is an estrous cycle-dependent fluctuation in the display of CD in female hamsters and suggests that increased estradiol might contribute to increased submissive behavior. We then demonstrated that ovariectomized females given estradiol prior to CD testing exhibited significantly higher submissive behavior in the presence of a NAI suggesting that estradiol increases the expression of CD in female hamsters. We have also shown that castrated males that were singly housed for four weeks displayed significantly more submissive behavior than did their intact counterparts. Interestingly, castrated and intact males that were singly housed for 10 days prior to behavioral testing displayed similar behavior during CD testing. Together these data suggest that androgens and isolation modulate the display of CD in male hamsters. Finally, we examined brain activation following CD testing in defeated males and females (in diestrus 1 and proestrus). Defeated male and proestrous females exhibited increased Fos activation in the dorsal lateral septum and hypothalamic paraventricular nucleus relative to defeated diestrous 1 females. Diestrous 1 females exhibited increased Fos expression in the lateral bed nucleus of the stria terminalis compared with both defeated groups. Collectively, these data suggest that gonadal hormones and duration of individual housing modulate the display of CD in female and male hamsters and that those animals which display CD exhibit differences in patterns of neuronal activation than do those that do not display CD.
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Jean, Arnaud. "Plasticité moléculaire de l'aire pré-optique médiane de l'hypothalamus induite par l'expérience sexuelle chez la souris mâle". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066109/document.
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Les mâles sexuellement expérimentés présentent des modifications à long terme de l'arborisation dendritique, de modifications épigénétiques ainsi qu'une augmentation des niveaux d'expression de protéines associées à la neurotransmission glutamatergique et à la microglie dans l'aire pré-optique médiane (mPOA). En revanche, les concentrations plasmatiques et hypothalamiques en hormones stéroïdes ainsi que les propriétés du système nitrergique, connues pour être modulés par l'expérience sexuelle chez le rat, ne sont pas modifiées. Dans un second temps, l'implication de la voie de signalisation ERK1/2 dans la réponse comportementale associée à l'expérience sexuelle a été étudiée. Nous avons montré que cette voie de signalisation, activée dans la mPOA lors de l'accouplement, est potentialisée par l'expérience sexuelle. Nous avons ensuite démontré que son activation est possible par une action rapide (30 minutes) des stéroïdes. Enfin, nous avons montré que l'inhibition de la voie ERK1/2 avant un premier accouplement n'altère pas la mise en place de l'expérience sexuelle mais diminue de façon réversible la motivation sexuelle des mâles. Ainsi, l'expérience sexuelle est à l'origine de modifications structurales et biochimiques à long terme de la mPOA. Ces modifications, différentes de celles connues chez le rat, sont associées à une potentialisation de la voie de signalisation ERK1/2 activée de façon transitoires durant l'accouplement. Ces résultats mettent en évidence la nécessité d'élaborer un nouveau modèle, différent de celui établi chez le rat, permettant d'expliquer l'amélioration comportementale associée à l'expérience sexuelle chez la souris mâleSexually experimented males exhibit long term modifications of the dendritic arborization, epigenetic modifications and increased levels of microglia and glutamate associated protein within the hypothalamic medial preoptic area (mPOA). However, hypothalamic and plasmatic concentration of steroid hormones and the nitrergic system are not impacted, contrary to data obtained in rat.The involvement of the ERK1/2 signaling pathway in the induction of sexual experience has also been studied. We showed that ERK1/2 pathway was activated within the mPOA during mating. This activation was increased in sexually experienced males. Furthermore, we showed ex vivo on hypothalamic slices that sex steroids were capable of rapidly (30 min) activate this pathway. Finally, the inhibition of ERK1/2 phosphorylation before the first mating did not disrupt the induction of sexual experience but decreased sexual motivation in a reversible manner.Taken together, these results indicate that long lasting and transitory plasticity mechanisms leading to sexual experience are different between rat and mouse. This indicate the necessity to elaborate a new molecular model associated with the behavioral improvement induced by sexual experience in male mouse
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Darzy, Ken H. K. "Pharmacological and physiological studies of anterior·pituitary hormones secretion (GH, ACTH and TSH) in cranially irradiated adult cancer survivors with radiation-induced hypothalamic- pituitary dysfunction". Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.490184.
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THE UNIVERSITY OF MANCHESTER ABSTRACT OF THESIS submitted by Ken Darzy for the Degree of M.D. and entitled 'Pharmacological and physiological studies of anterior pituitary hormones secretion (GH, ACTH and TSH) in cranially irradiated adult cancer survivors with radiation-induced hypothalamic-pituitary dysfunction'. Month and Year of submission: June 2008. This thesis describes the dynamics of GH, ACTH/Cortisol and TSH/T4 secretion in adult cancer survivors irradiated for non-pituitary brain tumours or leukaemia. Stimulated and physiological hormonal secretions were studied simultaneously. It was shown that, in patients with severe radiation-induced GH deficiency diagnosed by failure to pass both the ITT and the GHRH + AST, pulsatile GH secretion and diurnal rhythm are preserved, yet with severe amplitude attenuation and an overall feminised pattern of GH secretion characterized by relatively higher inter-peak levels (tonic secretion) and increased secretory disorderliness, as measured by ApEn. Patients with normal individual peak GH responses to the ITT and the GHRH+AST still showed evidence of damage to the h-p axis, as the overall mean GH responses were reduced by 50%. However, spontaneous fed and fasting GH secretion in this group was fully maintained both individually and at a group level compared with a matched control group. This finding argues against the previously held belief that somatotroph dysfunction is primarily due to radiation-induced GHRH deficiency, as the combined effect of reduced GHRH and secondary somatotroph atrophy would be expected to result in reduced spontaneous GH secretion. It was, therefore, concluded that radiation causes direct pituitary damage and that endogenous hyperstimulation of the h-p axis mediated by a compensatory increase in GHRH release restores normality of GH secretion in these patients with partially damaged somatotrophic axis (compensated GHD). Based on the findings in some patients, it was also suggested that 'near maximal' endogenous hyper-stimulation and GHRH release may limit further stimulation with the ITT, so much so, that a failed ITT response can occur in the presence of normal GHRH+AST response and normal spontaneous GH secretion. . These findings in adults has lead to the suggestion that failure of the hyperstimulated partially damaged h-p axis to increase GH secretion during periods of increased demand, such as growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction. It was reasonable to conclude that unlike the ITT, a failed response to the GHRH+AST almost always indicated GHD in the irradiated adult. On the contrary, failure to pass the ITT reflects 'a potential failure of the h-p axis to respond to increased demands and therefore it should remain the gold standard guide for the need for GH replacement therapy in children. Adult cancer survivors with normal ACTH reserve indicated by normal cortisol responses to the ITT have showed parallel and significant increases in fed and fasting 24-hour integrated cortisol concentrations and secretion rates with no change in half-life. This has been attributed to a pro-active h-p-adrenal axis with increased CRH-ACTH release mediated by the direct effects of radiation on the axis or perhaps the higher level of chronic stress in cancer survivors. In addition, euthyroid adult cancer survivors have significantly increased stimulated and integrated 24-hour TSH levels, especially in spinally irradiated patients with severe GHD. There was no change in the TSH bioactivity and the increase in TSH levels could be attributed to subclinical thyroidal damage, GHD-induced reduction in somatostatin tone and/or radiation-induced reduction in somatostatin and dopamine tone. The maximum TSH surge in the. 24-hour profile was slightly but significantly reduced. The subnormal nocturnal TSH surge seen in some patients reflected a shift in the timing of the peak and/or nadir TSH levels rather than a genuine loss of the TSH diurnal rhythm, as similarly seen in some normal individuals. This finding argues against the existence of so-called hidden central hypothyroidism. In summary, this thesis has provided novel insights into the pathophysilogy and site of radiation damage and its relevance to the clinical application ofthe diagnostic tests currently in use.
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Christian, Mark. "Investigation of the influence of sex steroid hormones and potential endocrine disrupting chemicals on developing rat hypothalamic dopaminergic neurones in vitro and in vivo". Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327047.
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Brischoux, Frédéric. "Etude ontogénétique du système à hormone de mélano-concentration (MCH) chez le rat et régionalisation de l'hypothalamus". Besançon, 2002. http://www.theses.fr/2002BESA0006.
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Kumarnsit, Ekkasit. "Hypothalamic actions of growth hormone secretagogues". Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/24795.
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In this study, the rat hypothalamic brain areas; the arcuate nucleus and the ventromedial hypothalamic nucleus, were selected for study of GHRP-6 and L-144,446 effects in vitro. Extracellular recordings showed that electrical activity of neuronal population in the arcuate nucleus was significantly excited by GHRP-6 and L-144,446. Patterns of excitation by either GHRP-6 or L-144,446 were closely similar. The increase in firing rate was observed with latency period of approximately 2 to 5 min. The excitation was sustained for more than 1 h after the secretagogue washout. Interestingly, GHRF-6 was also observed to increase the firing activity of neurones in the ventromedial hypothalamic nucleus. Patterns of increase in firing activity of ventromedial hypothalamic neurones were very similar to those observed in arcuate neurones. This is surprising, because in in vivo studies, Fos protein induction by systemic administration of secretagogues was consistently observed in the arcuate nucleus but not in the ventromedial hypothalamic nucleus. According to our evidence that ventromedial hypothalamic neurones were significantly excited to GHRP-6 in vitro, it was hypothesised that, in vivo, GHRP-6 stimulates neurones in the arcuate nucleus or other nuclei nearby which project their nerve endings to inhibit ventromedial hypothalamic neurones. The majority of neurones in the arcuate nucleus and the ventromedial hypothalamic nucleus that were excited by either L-144,446 or GHRP-6, were significantly inhibited by neuropeptide Y (NPY). Especially in the ventromedial hypothalamic nucleus, 68~% of GHRP-6-excited neurones, compared to 40% of those in the arcuate nucleus, were clearly inhibited by NPY, NPY is a potent orexigenic agent that was previously found to be produced in many neurones in the ventromedial arcuate nucleus. In addition, the existence of a NPY pathway that originates in the arcuate nucleus and projects to the ventromedial hypothalamic nucleus has previously been demonstrated. These results suggest that, in vivo, secretagogues may stimulate NPY neurones in the arcuate nucleus which project their nerve endings to inhibit a sub-population of the ventromedial hypothalamic nucleus. To investigate the mechanism of GHRP-6 action, immunohistochemistry technique was used to detect the induction of Fos, a protein product of the immediate early gene c-fos a protein product of the immediate early gene c-fos, in the accurate nucleus. The results showed that intravenous injection of GHRP-6 significantly increased immunostaining of Fos in the arcuate nucleus. Pretreatment with intravenous administration of NPY caused 61% reduction of number of Fos-positive neurones in the arcuate nucleus induced by GHRP-6. This findings confirm the effects of GHRP-6 on the electrical activity of the arcuate nucleus and support the idea that this brain area is a central site of action of GHRP-6. This thesis describes site of action of secretagogues in the hypothalamus with in vitro and in vivo data. It also shows the functional involvement of NPY in effects of secretagogues on firing activity and induction of Fos protein in this area.
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Osterstock, Guillaume. "Hypothalamic defaults after traumatic brain injury". Thesis, Montpellier 1, 2012. http://www.theses.fr/2012MON1T017/document.
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Les travaux de cette thèse ont porté sur le contrôle des neurones à GHRH dans des conditions physiologiques et pathologiques. Le but étant de caractériser les mécanismes cellulaires et moléculaires impliqués dans le fonctionnement ou dérégulations du réseau de neurones à GHRH. Ces neurones sont les principaux stimulateurs de la libération de l’hormone de croissance (GH). Nous avons d’abord montré que l’axe de la croissance et de l’appétit peuvent être régulés indépendamment au niveau de l’hypothamus. En effet, la ghréline, seule hormone produite par le tractus gastro-intestinal et connue pour stimuler la libération de GH en agissant principalement sur les neurones GHRH, stimule ces derniers de manière uniquement directe. Ces effets sont indépendants de ceux qu’elle exerce sur les neurones voisins à NPY, orexigéniques. De plus, la ghréline et les GHS (agonistes sélectifs du récepteur de la ghréline) ne changent pas le mode de décharge électrique des neurones à GHRH ni ne les synchronise. Enfin, ces effets ne présentent pas de dimorphisme sexuel. Dans un second temps, la somatostatine, principal inhibiteur de l’axe GH, induit un rythme d’activité électrique des neurones à GHRH médié par les récepteurs de sous-type SST1 et SST2. Ces effets sont donc temps-dépendants, et aussi sexuellement dimorphiques. Ils sont probablement impliqués dans la modulation de la pulsatilité ultradienne de la libération de GH. Enfin, après un traumatisme crânien, nous observons un déficit de la libération de GH qui apparaît tôt et est soutenu, comme ceux observés chez l’humain. Aucune inflammation ni changement histologique n’a été observe dans l’hypophyse. Cependant, l’inflammation, impliquant une réaction tanycytaire, microgliale, astrocytaire, est présente dans le noyau arqué et l’éminence médiane (EM), ou sont respectivement présents les corps cellulaires et terminaisons des neurones à GHRH. Ceci est lié à des changements morpho-fonctionnels de l’EM (augmentation perméabilité, rupture des barrières tanycytaires). Aucun changement n’a été observé dans le noyau périventriculaire, où sont localisés les neurones à somatostatine. Enfin, les propriétés électriques passives des neurones à GHRH ne sont pas modifiées. En conclusion, une dérégulation de leur activité au niveau des terminaisons nerveuses doit expliquer les défauts posttraumatiques de libération de GHThe works of this thesis were interested in the control of the hypothalamic GHRH neurons in physiological and pathological conditions. The goal was to clarify the molecular and cellular mechanisms involved in the control or impairments of GHR neuronal network functions. These neurons are the main stimulators of the GH release. We first showed that the hypothalamic growth axis could be regulated independently from the feeding network. Indeed, GHRH neurons are directly stimulated by ghrelin, which is the only hormone produced by the gastrointestinal tract known to stimulate the GH release through acting mainly on GHRH neurons. These effects are independent from its orexigenic effects exerted on the neighbourings NPY neurons. In addition, ghrelin and GHS (synthetic ghrelin receptor agonists) don’t change neither the firing rate of GHRH neurons, nor synchronize them. These effects are not gender-dependant; by contrast, Somatostatin, the major GH axis inhibitor, generates a sexual dimorphic and rhythmic inhibition of the GHRH neurons electrical activity mediated by its SST1 and SST2 receptors subtypes. These effects are so time-dependant direct and indirect effects and can probably be involved in the generation of the ultradian rhythm of the GH release. After a traumatic brain injury, we found an early and sustained deficiency of the GH release, like those observed in human. No pathological changes are visible in the pituitary gland. Inflammation occurs at the arcuate nucleus, and mainly at the median eminence levels; it involves a strong astrocyte reaction, tanycytes, and microglial and (or) infiltrated immune cells activations. These changes elicit morpho-functional impairments of the median eminence, permeability and leakage of the tanycyte barrier between the blood, CSF and Arc; at the opposite, nothing occur at the periventricular level, where are located SST neurons. Neither the number of GHRH neurons, neither their passive electrophysiological properties changed. Impairments of the activities of the GHRH nerve terminals, maybe associated to impairments of their regulated activity, must explain a GH deficiency
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Danzer, Steven Craig 1970. "Steroid hormone regulation of neurons in the hypothalamic arcuate nucleus". Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282605.
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Menopause is accompanied by neuronal hypertrophy and increased neurokinin B (NKB) gene expression in the human infundibular (arcuate) nucleus. We have hypothesized that these changes are secondary to withdrawal of gonadal steroids. In the present study, a rat model is used to determine if orchidectomy and hormone replacement alter the size and gene expression of arcuate NKB neurons. Compared to intact animals, gonadectomy significantly increased the mean profile area and number of neurons/section expressing NKB mRNA in the rat arcuate nucleus. Both the increase in NKB neuron size and number of neurons was prevented by implantation of estradiol- or testosterone-containing capsules. These data provide strong support for the hypothesis that the hypertrophy and increased numbers of neurons expressing NKB gene transcripts in postmenopausal women are secondary to ovarian failure. Studies were also conducted to determine if the conditions that induce neuronal hypertrophy and enhanced gene expression in the arcuate nucleus are accompanied by other morphological changes. To achieve this end, a fixed slice preparation was used to examine the morphology of neuroendocrine neurons in the rat arcuate nucleus. In comparison to intact controls, arcuate neuroendocrine neurons in the orchidectomized group had significantly larger somatic profile areas and exhibited significant increases in dendrite length, dendrite volume, terminal branch number, and spines per unit length of dendrite. These results provide evidence for hormonal regulation of dendritic morphology of arcuate neuroendocrine neurons in adult mammals. To assess the role of testosterone withdrawal in inducing these dendritic changes, hormone replacement studies were conducted. Testosterone treatment of castrate animals prevented increases in dendrite length and volume when compared to untreated castrate rats. Testosterone treatment also prevented the castration induced increase in the number of branches per dendrite. Finally, immunohistochemical studies indicate that approximately 22% of arcuate neuroendocrine neurons contain estrogen receptors, while 16% contain androgen receptors, indicating that these neurons can respond directly to changes in steroid hormone levels. These findings clearly demonstrate a role for testosterone in modulating the dendritic morphology of arcuate neuroendocrine neurons in adult rats.
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Machado, Carla de Moraes. "Alterações na expressão do Hormônio Concentrador de Melanina (MCH) na área hipotalâmica lateral do rato ao longo do desenvolvimento pós-natal e envelhecimento /". Botucatu, 2015. http://hdl.handle.net/11449/128083.
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Orientador: José de Anchieta de Castro e Horta JuniorCoorientador: Jackson Cioni Bittencourt
Banca: Luiz Fernando Takase
Banca: Luciana Pinato
Resumo: O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas...
Abstract: The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ...
Mestre
15
Machado, Carla de Moraes [UNESP]. "Alterações na expressão do Hormônio Concentrador de Melanina (MCH) na área hipotalâmica lateral do rato ao longo do desenvolvimento pós-natal e envelhecimento". Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/128083.
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O hormônio concentrador de melanina (MCH) do rato é um nonadecapeptídeo presente em neurônios localizados, principalmente, na área hipotalâmica lateral (LHA) que se projetam para diversas regiões do neuro-eixo. O MCH está envolvido em diversas funções, tais como: reprodução, certos aspectos do comportamento motivado, atividade locomotora, percepção sensorial, controle de temperatura, memória, aprendizagem, ansiedade, ciclo sono-vigília e comportamento alimentar. Nesse, o MCH atua como neuropeptídeo orexígeno. Durante o envelhecimento, ocorre a diminuição no consumo de energia associada à idade. Nesse trabalho, analisamos em diferentes faixas etárias, as variações da expressão do MCH na área hipotalâmica lateral, empregando métodos esterológicos (para estimar o número de neurônios MCH-ir, área, volume e densidade neuronal), reconstrução tridimensional (para estudo da distribuição dos neurônios MCH-ir) e densitometria óptica de tecido hibridizado para reconhecimento do RNAm do ppMCH (para mensuração da área hibridizada, densidade óptica média e densidade óptica integrada [DOI]) na LHA e em suas regiões. Foram utilizados 35 ratos Sprague-Dawley machos, divididos em 7 grupos experimentais de diferentes idades: 14 (lactente), 28 (pré-púbere), 50 (púbere), 90 (adulto jovem), 210 (adulto maduro), 540 (adulto senescente) e 750 (adulto senil) dias pós-natais. Os animais foram submetidos à perfusão transcardíaca, seus encéfalos coletados e processados para análise da expressão do MCH na área hipotalâmica lateral, segundo protocolos de imuno-histoquímica e hibridização in situ. A LHA apresentou um aumento significativo no número de neurônios apenas entre os grupos de 14 e 28 dias e sua área e volume foram significativamente menores apenas no grupo de 14 dias em relação a todos os grupos, com exceção do grupo de 750 dias. No entanto, com relação a densidade neuronal não foram observadas...
The Melanin-Concentrating Hormone (MCH) is a nonadecapeptide located mainly in neurons in the lateral hypothalamic area (LHA), which innervate several regions of neuraxis. MCH is involved in many functions as reproduction, aspects of motived behaviors, motor activity, sensorial information, temperature control, memory, learning, anxiety, sleep-wake cycle and feeding behavior in which the MCH plays an orexigenic role. The energy consumption in aging is reduced as well as, the expression of MCH presents alterations associated with age. Therefore, we analyzed the variations in the expression of MCH at different ages in the lateral hypothalamic area, using stereology (to estimate the number of MCH-ir neurons, area, volume and neuronal density), 3D reconstruction (to study the distribution of MCH-ir neurons) and optical density after in situ hybridization protocol for ppMCH RNAm (to measure the hibridizated area, the mean optical density and the integrated optical density [IOD]) in the LHA and its three regions. In this study, 35 animals were divided in 7 experimental groups of 14 (neonate), 28 (prepubescent), 50 (pubescent), 90 (young adult), 210 (middle aged adult), 540 (senescent adult) and 750 (elderly adult) postnatal days. All the animals were perfused via the ascending aorta, the brains were collected and processed by immunohistochemistry and in situ hybridization protocols to analyze the expression of MCH in the lateral hypothalamic area. LHA neurons number increased only between groups of 14 and 28 days, and its area and volume significantly smaller in 14-days group when in respect to all other groups but the 750-days one. However, there weren't differences in neuronal density among groups. MCH-ir neurons distribution in LHA and contiguous regions was similar among all groups as well. Hypothalamic MCH-ir neurons has shown uniform rates in and out of LHA, but after analyzing its distribution in mamillary, tuberal and anterior ...
FAPESP: 2013/08618-3
16
Miller, Robert. "Approaches to the parametric modeling of hormone concentrations". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-118882.
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Transdisciplinary research in general, and stress research in particular, requires an efficient integration of methodological knowledge of all involved academic disciplines, in order to obtain conclusions of incremental value about the investigated constructs. From a psychologist’s point of view, biochemistry and quantitative neuroendocrinology are of particular importance for the investigation of endocrine stress systems (i.e., the HPA axis, and the SNS). Despite of their fundamental role for the adequate assessment of endocrine activity, both topics are rarely covered by conventional psychological curriculae. Consequently, the transfer of the respective knowledge has to rely on other, less efficient channels of scientific exchange. The present thesis sets out to contribute to this exchange, by highlighting methodological issues that are repeatedly encountered in research on stress-related endocrine activity, and providing solutions to these issues.
As outlined within this thesis, modern stress research tends to fall short of an adequate quantification of the kinetics and dynamics of bioactive cortisol. Cortisol has gained considerable popularity during the last decades, as its bioactive fraction is supposed to be reliably determinable from saliva and is therefore the most conveniently obtainable marker of HPA activity. However, a substantial fraction of salivary cortisol is metabolized to its inactivated form cortisone by the enzyme 11β-HSD2 in the parotid glands, which is likely to restrict its utility. Although the commonly used antibody-based quantification methods (i.e. immunoassays) might “involuntarily” qualify this issue to some degree (due to their inherent cross-reactivity with matrix components that are structurally-related to cortisol; e.g., cortisone), they also cause differential within-immunoassay measurement bias: Salivary cortisone has (as compared to salivary cortisol) a substantially longer half-life, which leads to an overestimation of cortisol levels the more time has passed since the onset of the prior HPA secretory episode, and thus tends to distort any inference on the kinetics of bioactive cortisol. Furthermore, absolute cortisol levels also depend on the between-immunoassay variation of antibodies. Consequently, raw signal comparisons between laboratories and studies, which are favorable as compared to effect comparisons, can hardly be performed. This finding also highlights the need for the long-sought standardization of biochemical measurement procedures. The presumably only way to circumvent both issues is to rely on quantification of ultrafiltrated blood cortisol by mass-spectrometric methods.
Being partly related to biochemical considerations with research on HPA activity, a second topic arises concerning the operationalization of the construct itself: In contrast to the simple outcome measures like averaged reaction times, inclined stress researchers can only indirectly infer on the sub-processes being involved in HPA activity from longitudinally sampled hormone concentrations. HPA activity can be quantified either by (a) discrete-time, or by (b) continuous-time models. Although the former is the most popular and more convenient approach (as indicated by the overly frequent encounter of ANOVAs and trapezoidal AUC calculations in the field of psychobiological stress research), most discrete time models form rather data-driven, descriptive approaches to quantify HPA activity, that assume the existence of some endocrine resting-state (i.e., a baseline) at the first sampling point and disregard any mechanistic hormonal change occurring in between all following sampling points. Even if one ignores the fact, that such properties are unlikely to pertain to endocrine systems in general, many generic discrete time models fail to account for the specific structure of endocrine data that results from biochemical hormone measurement, as well as from the dynamics of the investigated system. More precisely speaking, cortisol time series violate homoscedasticity, residual normality, and sphericity, which need to be present in order to enable (mixed effects) GLM-based analyses. Neglecting these prerequisites may lead to inference bias unless counter-measures are taken.
Such counter-measures usually involve alteration of the scale of hormone concentrations via transformation techniques. As such, a fourth-root transformation of salivary cortisol (being determined by a widely used, commercially available immunoassay) is shown to yield the optimal tradeoff for generating homoscedasticity and residual normality simultaneously. Although the violation of sphericity could be partly accounted for by several correction techniques, many modern software packages for structural equation modeling (e.g., Mplus, OpenMX, Lavaan) also offer the opportunity to easily specify more appropriate moment structures via path notation and therefore to relax the modeling assumptions of GLM approaches to the analysis of longitudinal hormone data.
Proceeding from this reasoning, this thesis illustrates how one can additionally incorporate hypotheses about HPA functioning, and thus model all relevant sub-processes that give rise to HPA kinetics and dynamics. The ALT modeling framework being advocated within this thesis, is shown to serve well for this purpose: ALT modeling can recover HPA activity parameters, which are directly interpretable within a physiological framework, that is, distinct growth factors representing the amount of secreted cortisol and velocity of cortisol elimination can serve to interpret HPA reactivity and regulation in a more unambiguous way, as compared to GLM effect measures. For illustration of these advantages on a content level, cortisol elimination after stress induction was found to be elevated as compared to its known pharmacokinetics. While the mechanism behind this effect requires further investigation, its detection would obviously have been more difficult upon application of conventional GLM methods. Further extension of the ALT framework allowed to address a methodological question, which had previously been dealt with by a mere rule of thumb; what’s the optimal threshold criterion, that enables a convenient but comparably accurate classification of individuals whose HPA axis is or is not activated upon encountering a stressful situation? While a rather arbitrarily chosen baseline-to-peak threshold of 2.5 nmol/L was commonly used to identify episodes of secretory HPA activity in time series of salivary cortisol concentrations, a reanalysis of a TSST meta- dataset by means of ALT mixture modeling suggested that this 2.5 nmol/L criterion is overly conservative with modern biochemical measurement tools and should be lowered according to the precision of the utilized assay (i.e., 1.5 nmol/L).
In sum, parametric ALT modeling of endocrine activity can provide a convenient alternative to the commonly utilized GLM-based approaches that enables the inference on and quantification of distinct HPA components on a theoretical foundation, and thus to bridge the gap between discrete- and continuous-time modeling frameworks. The implementation of the outlined modeling approaches by the respective statistical syntaxes and practical guidelines being derived from the comparison of cortisol assays mentioned above, are provided in the appendix of the present thesis, which will hopefully help stress researchers to directly quantify the construct they actually intend to assess.
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Baines, Elizabeth. "Photoperiodic control of hypothalamic gonadotrophin releasing hormone mRNA in Japanese quail". Thesis, University of Edinburgh, 2001. http://hdl.handle.net/1842/10704.
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The research presented in this Thesis investigated the relationship between hypothalamic gonadotrophin releasing hormone-I (GnRH-I) gene expression and the photoperiodic control of reproduction in the Japanese quail (Coturnix c. japonica). A cDNA encoding quail GnRH-I was cloned and used to develop a competitive RT-PCR assay for GnRH-I mRNA. The assay was validated and used to quantify levels of GnRH-I mRNA in the hypothalamus in a series of photoperiodic experiments. The first question addressed was whether a change in GnRH-I mRNA is involved in photoinduced luteinising hormone (LH) secretion, as inferred from an increase in blood plasma LH after transfer from short to long days. An increase in plasma LH was first seen 20h after dawn of the first long day and was found to be associated with an increase in hypothalamic GnRH-I mRNA. Exposure to one photostimulatory day followed by a return to short days, stimulated a surge of LH secretion which persisted for up to 10 days. This photo-induced carry “over effect” for LH secretion was not associated with a “carry over” effect for increased GnRH-I mRNA. The second question addressed was whether the development of relative photorefractoriness induced by prolonged exposure to long day lengths is associated with a change in hypothalamic GnRH-I mRNA. Relative photorefractoriness was demonstrated by showing that quail maintained on long days (18 hr light/day) for a prolonged period went out of breeding condition when transferred to 13 hr light/day, a photoperiod which is photo-stimulatory for fully photosensitive quail. The development of relative photorefractoriness in quail held on 18hr light/day was not associated with a decrease in plasma LH but was associated with a decrease in hypothalamic GnRH-I mRNA. Since the development of relative photorefractoriness is associated with increased prolactin secretion, a final series of experiments investigated the possibility that prolactin might exert an inhibitory effect on hypothalamic GnRH-I mRNA. Treatment of quail with ovine prolactin for 5 days after photostimulation suppressed the photo-induced increase in GnRH-1 mRNA.
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Bueno, Débora Nunes Martins. "Estudo das conexões da área incerto-hipotalâmica relacionadas ao controle neuroendócrino". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-03062014-164739/.
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A área incerto-hipotalâmica (IHy) é uma região diencefálica que atua em funções reprodutivas através da presença do hormônio concentrador de melanina (MCH). Nosso objetivo é estudar as conexões da IHy de fêmeas com áreas relacionadas ao controle neuroendócrino reprodutivo, usando traçador anterógrado dextrana amina biotinilada (BDA) e retrógrado Fluorogold (FG). Nesse sentido, destacamos que a IHy, em fêmeas, conecta-se reciprocamente com diversos núcleos hipotalâmicos da região periventricular e pré-óptica, além das áreas hipotalâmica anterior, posterior e lateral. Nosso resultados também sugerem um dimorfismo sexual das projeções da IHy, já que a área pré-óptica medial, o núcleo anteroventral periventrciular e o núcleo arqueado são mais densamente inervadas pelas IHy em fêmeas do que em machos.The incerto-hypothalamic area (IHy) is a diencephalic region poorly studied which is characterized by two non-colocalized neurochemical groups composed by the A13 dopaminergic group intermingled with predominantly GABAergic cells co-expressing melanin-concentrating hormone (MCH) and/or cocaine and amphetamine regulated transcript (CART). Functional studies suggest that IHy is involved in the neuroendocrine control of female reproduction in specific metabolic states mediated by MCH. In this way, our aim is to study the IHy connections in female rats related to neuroendocrine control of female reproduction using neuronal anterograde Biotin Dextran Amine (BDA) and retrograde Flurogold (FG) tracers. As a result, we found that IHy projections are the lateral septal nucleus, bed nucleus of stria terminalis, paraventricular thalamic nucleus, reuniens thalamic nucleus, medial preoptic area, medial and lateral preoptic nucleus, median preoptic nucleus, periventricular hypothalamic nucleus, anteroventral periventricular nucleus, anterior, posterior and lateral hypothalamic area and precommissural nucleus. The main afferents to the IHy, in females, are the lateral septal nucleus, median preoptic nucleus and paraventricular thalamic nucleus. These results suggest sexually dimorphic projections from the IHy, since IHy more densely innervates neuroendocrine regions in female than in male rats.
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Pithey, Anne Louise. "Autocrine regulation of gonadotropin-releasing hormone in immortalized hypothalamic GT1-7 neurons". Master's thesis, University of Cape Town, 1994. http://hdl.handle.net/11427/27030.
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The existence of an ultrashort feedback mechanism regulating GnRH secretion has been supported from in vivo and in vitro studies. However, the complex synaptic connections of GnRH neurons with other neural elements made it difficult to determine whether the regulation was mediated by direct actions on the GnRH neurons or through actions on other interneurons. The recent development of the GnRH-secreting neuronal cell line, GT1, provided a model system for the study of neural regulation of a pure population of GnRH neurons. The present studies utilized GT1 -7 cells to investigate whether GnRH (at the level of the nerve terminal) influences the control of its own release. Preliminary studies determined the presence of GnRH mRNA in GT1-7 cells and established a cell culture system for the analysis of secretagogue-induced GnRH release. In this system GnRH release was shown to be spontaneous and was enhanced by the addition of K⁺, L-GLU, forskolin and PMA. Furthermore, K⁺- and forskolin-induced GnRH release was dependent on extracellular Ca²⁺. For the analysis of an ultrashort feedback mechanism, GT1-7 cells were cultured in 6-well plates to near confluence and then incubated in serum-free medium in the presence (1 nM- 1 μM) or absence of GnRH antagonist, Ant 27. Basal, K⁺-and forskolin-induced secretion of GnRH was monitored with antiserum 1076 which does not cross-react with Ant 27 at> 1 μM. Ant 27 treatment increased basal, K⁺- and forskolin-stimulated GnRH release in a dose-dependent manner. Total content was unaffected by 18 h treatment of GT1-7 cells with Ant 27. This suggests that the effects of Ant 27 are at the level of release and not biosynthesis. The presence of GnRH binding sites in the cells was demonstrated with ¹²⁵I-GnRH analog. These findings support the concept that GnRH, acting via autoreceptors, negatively controls its own release.
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Bronner, Sandra. "Le système ocytocinergique hypothalamo-spinal : étude anatomique et fonctionnelle". Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13077.
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L'ocytocine (OT), outre ses actions hormonales classiques, exerce des effets de type neurotransmetteur et/ou neuromodulateur dans plusieurs régions du système nerveux central, dont la moelle épinière. L'application des techniques d'autoradiographie sur plans-films (détection macroscopique) et sur lames émulsionnées (détection à l'échelle cellulaire) permet l'étude des sites de liaison de l'OT dans la moelle épinière. Ces sites sont exprimés dans des régions sensorielles (laminae I et II, noyau latéral spinal) et autonomes (lamina X, colonnes intermédiolatérales, noyau parasympathique sacré). Alors que ceux des régions sensorielles sont déjà présents à la naissance, ceux des régions autonomes n'apparaissent que dans les premières semaines de vie postnatale. Une expression transitoire est observée dans le noyau dorsal et sur des motoneurones des cornes ventrales durant les deux premières semaines. La densité des sites de liaison dans les couches superficielles des cornes dorsales varie significativement durant les trois premières semaines et présente un maximum à 14 jours. Les modifications expérimentales du taux de stéroïdes sexuels n'ont aucun effet significatif sur l'expression des sites de liaison de l'OT dans la moelle épinière. La détection immunocytochimique des fibres ocytocinergiques met en évidence leur présence dans les régions exprimant les sites de liaison de l'OT. Une étude de traçage antérograde depuis le noyau paraventriculaire de l'hypothalamus (NPV) montre qu'un neurone parvocellulaire peut projeter à la fois dans les régions sensorielles et autonomes de la moelle épinière. Une stimulation électrique du NPV conduit à une augmentation du nombre de neurones exprimant la protéine c-Fos dans les cornes dorsales de la moelle épinière, ces neurones sont en contact étroit avec les fibres ocytocinergiques. Ces résultats confortent l'existence d'un contrôle par l'OT des centres autonomes et nociceptifs de la moelle épinière via la voie paraventriculospinaleBesides its classical hormonal actions, the neurohypophyseal peptide oxytocin (OT) exerts neurotransmitter and/or neuromodulator actions in many regions of the central nervous system, including the spinal cord. Application of autoradiographic techniques either on films (macroscopic detection) or on liquid emulsion covered slides (detection at cellular scale) allows the precise study of OT binding sites localisation in the spinal cord during postnatal development. They are expressed in sensory (laminae I and II, lateral spinal nucleus) and autonomous regions (lamina X, intermediolateral columns, sacral parasympathetic nucleus). OT binding sites in sensory regions are already present at birth, whereas those of autonomous regions appear only during the first postnatal weeks of life. A transient expression of OT binding sites occurs in the dorsal nucleus and on motoneurones of the ventral horns during the first two weeks of life. Density of OT binding sites in the laminae I and II varies significantly during the first three weeks of life, presenting a maximum at day 14. Experimental modifications of the sexual steroids level have no significant effect on OT binding sites expression in the spinal cord. Immunocytochemical detection of oxytocinergic fibres reveals their presence in regions expressing OT binding sites. Anterograde tract tracing after biotin dextran amine injection in the paraventricular nucleus of the hypothalamus (NPV) followed by single fibres reconstruction clearly shows that some parvocellular neurones project at the same time in sensory and autonomous regions of the lumbosacral spinal cord. An electrical stimulation of the NPV leads to an increase in the expression of c-Fos protein in the dorsal horns. The c-Fos expressing neurones after NPV stimulation are in close vicinity with oxytocinergic fibres. These results comfort the existence of an oxytocinergic control of autonomous and nociceptive centres in the spinal cord via the paraventriculospinal tract
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Harbuz, M. S. "Hypothalamic catecholamines in the regulation of LH secretion in the domestic fowl (Gallus domesticus)". Thesis, University of Reading, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382172.
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MacGregor, Duncan James. "Modelling hypothalamic control of growth hormone release and spike firing in oxytocin cells". Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/23104.
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Toppila, Jussi. "Somatostatin, growth hormone-releasing hormone, galanin and their hypothalamic messenger ribonucleic acids in the regulation of sleep in rats". Helsinki : University of Helsinki, 1999. http://ethesis.helsinki.fi/julkaisut/laa/biola/vk/toppila/.
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Gulikers, Keven Peter. "Evaluation of the effects of clomipramine on the canine hypothalamic-pituitary-thyroid axis". Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/31768.
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Tricyclic antidepressants have been shown to alter thyroid function in man and laboratory animals, but have not been evaluated in the dog. The effect of administration of clomipramine on canine thyroid function was studied in a prospective protocol in which 14 mature, healthy dogs were administered clomipramine (3 mg/kg PO q12h) for 112 days. Thyroid-stimulating hormone (TSH), total thyroxine (T4), total 3,5,3' triiodothyronine (T3), free thyroxine (fT4), and 3,3',5' triiodothyronine (reverse T3; rT3) concentrations were measured on selected days. Thyrotropin-releasing hormone (TRH) response tests were performed concurrently. Repeated measures analysis of variance was applied to test for effects of day of treatment; when significance (p < 0.05) was noted, it was further investigated using orthogonal polynomial trends.
Significant decreases were found in serum T4 (26 ± 1.2 to 17 ± 0.5 nmol/L, p < 0.001), fT4, (29 ± 2.4 to 19 ± 1.3 pmol/L, p < 0.0002), and rT3 (1.2 ± 0.1 to 0.83 ± 0.08 nmol/L, p < 0.0001) concentrations. The effect of time on serum T3 concentration was also significant (p < 0.0001), but no consistent trend could be identified. No significant effect of time was noted in either pre- or post-TRH TSH concentrations.
The results of this study indicate that significant and substantial decreases in T4 (35%), fT4 (38%), and rT3 can occur during clomipramine administration. Long-term administration of clomipramine may result in a misdiagnosis of hypothyroidism if a dog is tested while taking this medication and, since decreased serum fT4 occurs, hypothyroidism may result.
Master of Science
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DiBenedetto, Lynn M. "An Examination of the Hypothalamo-neurohypophysial System of the Rat: Restoration of the Vasopressinergic System". eScholarship@UMMS, 1997. https://escholarship.umassmed.edu/gsbs_diss/169.
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The hypothalamo-neurohypophysial model has been studied for many years. Of note, when the axons of the magnocellular, peptidergic neurons of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are transected or crushed, varying degrees of polydipsia and polyuria ensue as the result of measurable losses of vasopressin (AVP) within the organism's circulation. Following insult, these hypothalamic cells show a remarkable capacity to reorganize themselves within the proximal areas of the infundibular stalk and median eminence and form what has come to be known as a new 'mini neural lobe' . While the surviving neurons sprout new projections toward the level of the external zone, vascular hypertrophy is marked throughout the new neurohypophysis and new neurohemal contacts have been identified (at the ultrastructural level) associated with these vessels. In parallel with this vascular hypertrophy is a measurable re-release of vasopressin into the circulation. This new 'mini neural lobe' now has the morphological and physiological appearance of an intact neural lobe and is capable of releasing AVP in response to changes in water balance.
While the ability of these axons to reorganize is more characteristic of the peripheral nervous system (PNS), this model system provides an unique opportunity to study axonal regeneration of the central nervous system (CNS). Not only the mechanisms underlying the restoration of AVP function following axotomy but the extent to which various magnocellular neuron populations are involved in the regenerative process may also be analyzed. Before attempting to identify putative markers associated with this regenerative process, it was necessary to carefully characterize the system following axonal injury. Using Sprague Dawley rats, we repeated previous physiological studies which had examined the intake of water and output of urine following hypophysectomy. In addition, we also correlated the restoration of water balance with the return of AVP release, as measured by radioimmunoassay. These data defined a temporal framework in which magnocellular AVP regeneration occurs.
As a result of repeating these physiological studies, we noted several inconsistencies between other previously published work. First, the time course of AVP recovery did not agree with other published results, nor did the first appearance of AVP immunoreactivity . We did not observe a complete recovery of water balance as previously reported and the degree of magnocellular death was inconsistent with other reports. In light of these many conflicting observations between several historical reports and our own results, we did a basic physiological re-characterization of the hypothalamo-neurohypohysial system following hypophysectomy. By means of immunohistochemistry, we also demonstrated the re-appearance of AVP within the new the 'mini neural lobe ' concomitant with the increased appearance of synapsin I, a marker associated with the presence of mature and presumably functioning synapses to be no sooner than 28 days following surgical removal of the hypophysis.
Immunocytochemistry was also used in conjunction with retrograde fluorescent labeling to extend the previous studies and include a 2-D analysis of cell survival throughout the PVN and SON following hypophysectomy or neurohypophysectomy. As reported previously, magnocellular neuronal loss is greater within the SON, particularly the hypophysectomized subject, and less so within the PVN; again with the greater loss in the PVN of the hypophysectomized animal. Based upon our observations and other recent reports, we suggest the possibility that some cells of the hypothalamo-neurohypophysial system or some other extrahypothalamic cell population may be capable of expressing vasopressin in response to neurohypophysectomy. We provide initial evidence that glial cells of the third ventricle may indeed be involved.
Finally, one of the ultimate goals of using this as a model system of CNS regeneration is to understand the underlying mechanisms and components essential to central nervous tissue regeneration. Toward that end I have been involved with the initial studies to optimize an adenovirus delivery system which will be capable of incorporating various putative neurotransmitter and/or peptide anti-sense messages, being injected into the neurohypophysis and transported back into the cells of the hypothalamo-neurohypophysial system. Once these antisense sequences are expressed by the cells following axotomy, the sequence of expression of various proteins in response to injury may be elucidated.
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Atallah-Ibrahim, Afnan. "Effects of sex steroid hormones on the neurovascular unit in the mouse hypothalamus". Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066199/document.
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L’intégrité fonctionnelle de la barrière hémato-encéphalique (BHE) est altérée dans de nombreuses pathologies neurologiques et métaboliques. Les vaisseaux cérébraux sont des tissus cibles des hormones stéroïdes sexuelles mais la contribution respective de ces effecteurs endocriniens et de leurs récepteurs dans l’intégrité de la BHE reste encore à être précisée. Les effets des hormones gonadiques sur l’unité neurovasculaire chez la souris ont été étudiés, en se concentrant sur l’aire préoptique médiane de l’hypothalamus, une région cérébrale hormono-sensible. L’augmentation de la perméabilité de la BHE chez des souris mâles et femelles gonadectomisés. Elle est associée chez le mâle à une désorganisation des jonctions serrées et une diminution de l’expression des protéines les constituant, à une activation des cellules gliales, et à une augmentation de l’expression de molécules inflammatoires, la supplémentation en testostérone permettant la restoration. Les récepteurs des androgènes et des estrogènes peuvent ainsi être impliqués dans la régulation hormono-dépendante du transport paracellulaire. La lignée de souris transgéniques sélectivement invalidées pour le récepteur neural des androgènes, a permis de mettre en évidence l’effet délétère de l’absence de ce récepteur sur l’intégrité de la BHE et des jonctions serrées. Pour compléter, un modèle ex vivo de tranches d’hypothalamus a permis d’appréhender les effets à court terme de la testostérone sur la BHE. Ces données soulèvent des questions sur les effets délétères potentiels des perturbateurs endo-criniens sur l'intégrité BBB et l'apparition de maladies neurologiques et métaboliques associéesFunctional integrity of the blood-brain barrier (BBB) is compromised in many neurological and metabolic pathologies. Cerebral blood vessels are target tissue for sex steroid hormones but the relative contribution of these endocrine effectors and their receptors in the BBB integrity are still unclear. Effects of gonadal hormones on the mouse neurovascular unit were studied, focusing on the hypothalamic medial preoptic area, a highly sensitive brain area to gonadal steroid hormones. BBB permeability increased in both gonactectomized male and female, is associated with tight junction disorganization and lower expression of tight junction proteins, glial activation, and up-regulation of inflammatory molecules in male. Testosterone supplementation restores the BBB impermeability, tight junction integrity, and almost completely abrogated the inflammatory features. Androgen and estrogen receptor may be involved in testosterone-induced regulation of the formation and maintenance of tight junction in males. Studying the involvement of these receptors using a trans-genic mice line selectively lacking neural AR in the CNS, highlighted the negative effect of this dele-tion on the BBB and TJ integrity. To complete, ex vivo slices of male mouse hypothalamus allowed to assess short-term molecular mechanisms of testosterone on the BBB structure and function.These data raise questions about the potential deleterious effects of endocrine disruptors on the BBB integrity and the occurrence of neurological and metabolic diseases
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Nesbitt, Catherine. "Variations in maternal lickinggrooming influences both dam and offspring's hypothalamic-pituitary-adrenal hormone profile". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111562.
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Pup directed maternal licking and grooming (LG) increases with corticosterone (CORT) supplimentation (Rees et al 2004). Increases in LG lead to an attenuation of the adult offspring's HPA response to stress (Liu et aI1997). Similarly, Neonatal increases in glucocorticoids lead, in adulthood, to the same attenuation of the HPA stress response (Catalani et aI1993). We hypothesize that dams exhibiting increased LG will have increased circulating CORT, and this increase will be reflected in their offspring. This thesis characterizes the HPA hormone profile adrenocorticotropic hormone (ACTH), CORT & Corticosterone Binding Globulin (CBG) in High LG (H) and Low LG (L) litters, 5 days postpartum (P4). Furthermore pup plasma CORT levels are determined at (P) 3,4,6,10 & 14. Finally P10 Hand L LG ACTH, CORT & CBG will be assessed after stress. RESULTS: H compared to L LG dams have significantly increased plasma CORT (p=0.03). At P4, H LG offspring have significantly increased plasma CORT (p=0.03) and significantly decreased plasma ACTH (p=0.04) as compared to L LG offspring. Plasma CBG levels are significantly lower in H compared to L LG offspring (p=0.01) at the same age. Across the Stress Hyporesponsive Period (SHRP) H LG offspring had significantly increased plasma CORT (p= 0.00) compared to L LG offspring at P3. Challenged with a stressor at P10, H LG offspring have an exaggerated plasma CORT response (p=0.00). This data suggests increases in plasma CORT in the dams leads to increased CORT in the high offspring, contributing perhaps to a more mature stress response at P10.Key word abbreviation: (1) CORT - CORTicosterone, (2) ACTH - AdrenoCorticoTropin releasing Hormone, (3) CBG - Corticosteroid Binding Globulin, (4) SHRP - Stress Hypo-Responsive Period, (5) P - Post-natal day, (6) HPA - Hypothalamic-Pituitary-Adrenal, (7) LG - Licking/Grooming, (8) ADX/OVX - ADrenalectomized/OVarectomized.
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Haynes, Andrea Claire. "Characterisation of orexins and melanin-concentrating hormone in the hypothalamic regulation of food consumption". Thesis, University of Buckingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250767.
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Barbotin, Anne-Laure. "Plasticité neuro-structurale de l’hypothalamus dans le syndrome des ovaires polykystiques". Thesis, Lille, 2019. http://www.theses.fr/2019LILUS043.
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L’hormone anti-Müllerienne (AMH) dont les taux dans le sérum sont élevés dans le Syndrome des Ovaires Polykystiques (SOPK) est connue pour augmenter la sécrétion de LH/GnRH. Comme mis en évidence récemment, cette augmentation de la sécrétion de GnRH pourrait être liée à une hyperactivité des neurones à GnRH en réponse à une action directe de l’AMH mais pourrait également s’exercer indirectement via une augmentation des afférences excitatrices sur les neurones à GnRH. Par ailleurs, les tanycytes, qui enchâssent les terminaisons des neurones à GnRH, expriment le récepteur à l’AMH et sont connus pour moduler la plasticité neuro-structurale de l’hypothalamus. Ainsi, notre objectif est de tester les deux hypothèses suivantes dans un modèle animal et chez la femme. Est-ce que la physiopathologie du SOPK : 1- Est liée à une rétraction des tanycytes provoquée par l’AMH, entraînant l’augmentation des sécrétions de GnRH / LH ? Et/ou 2- Est liée à une augmentation de l’activité des neurones à GnRH AMH-dépendante ?Nous avons étudié la modification de la plasticité morphologique de l’hypothalamus en microscopie électronique en comparant la distance entre les terminaisons des neurones à GnRH et l’espace péri-capillaire entre des éminences médianes de rates en phase de dioestrus de leur cycle oestral (au moment où ces terminaisons sont normalement enfouies par les tanycytes) traitées par de l’AMH et des contrôles. Puis, nous avons comparé cette même distance entre des éminences médianes issues d’un modèle de souris SOPK en comparaison à des contrôles. Enfin, nous avons étudié la plasticité neuro-structurale de l’hypothalamus chez des femmes SOPK et des témoins par une approche en imagerie en comparant les métabolites cérébraux.Nous avons observé une augmentation significative du nombre de terminaisons de neurones à GnRH situées à proximité de l’espace péri-capillaire dans le groupe traité par l’AMH par rapport aux contrôles et nous avons fait les mêmes observations chez les souris SOPK comparées aux contrôles. Par ailleurs, nous avons mis en évidence une augmentation de l’activité neuronale dans le noyau arqué de l’hypothalamus chez des souris SOPK. Or, cette région est particulièrement impliquée dans la régulation de la sécrétion de GnRH. Chez les femmes atteintes de SOPK, nous avons pour la première fois mis en évidence des concentrations plus élevées de GnRH mesurées par spectroscopie de masse par rapport à des femmes normo-ovulantes. Notre étude par IRM, chez les femmes SOPK et contrôles, vient conforter ce résultat en montrant une augmentation de la viabilité/activité neuronale. Cette étude translationnelle suggère que l’augmentation des sécrétions de GnRH/LH rencontrées dans le SOPK serait dépendante d’une part d’un rapprochement de terminaisons à GnRH à l’espace péri-capillaire et d’autre part d’une augmentation de l’activité neuronale hypothalamiquePolycystic ovary syndrome (PCOS) is the most common reproductive disorder (10% of women worldwide). Anti-Müllerian hormone (AMH) levels are found to be 2-3-fold higher in PCOS women than in those with normal ovaries. AMH induces LH secretion by stimulating the activation of GnRH secretion. As recently demonstrated, this increase in GnRH secretion could be related to hyperactivity of GnRH neurons in response to a direct action of AMH but could also be exerted indirectly via an increase in excitatory inputs on GnRH neurons.Our team has previously demonstrated that tanycytes, which unsheathe the terminals of GnRH neurons, regulate GnRH secretion and express AMH receptor. Thus, we aim to determine (1) whether elevated AMH could be responsible for the retraction of the tanycyte coverage leading to increased GnRH/LH secretion in PCOS and (2) whether neuronal hyperactivity in hypothalamus could contribute to higher GnRH activity in PCOS women.Firstly, we have performed ultrastructural studies in rodents’ median eminence (ME) explants challenged with AMH. Then, we compared tanycytic retraction using electron microscopy. We have performed the same experiments in a PCOS mouse model. In humans, we have used metabolic magnetic resonance imaging approaches (i.e. proton magnetic resonance spectra). In order to assess neuronal activity, we have compared N-acetyl-aspartate/creatine ratios in the hypothalamus between PCOS women versus controls.Using electron microscopy, we have shown that tanycytes displayed a significant retraction of their end-feet after AMH treatment ex vivo. This is followed by the sprouting of GnRH terminals towards the pericapillary space. Such processes could significantly favor the sustained delivery of peak levels of GnRH, which could contribute to the rise in LH levels typical of PCOS condition. We have found the same results in PCOS-mouse model with higher GnRH terminals towards the pericapillary space in PCOS mice than in controls. In addition, we found an increase in neuronal activity in the arcuate nucleus of the hypothalamus in PCOS mice. Moreover, this region is particularly involved in the regulation of GnRH secretion. For the first time, we have demonstrated that PCOS women exhibit higher concentrations of GnRH measured by mass spectroscopy than GnRH levels in normo-ovulatory women. Our proton magnetic resonance spectroscopy analysis has revealed that PCOS women exhibit higher N-acetyl aspartate/creatine ratio than controls. These results are predicted to be correlated with increased hypothalamic activity.This translational study suggests that the increase in GnRH / LH secretions found in PCOS could be explained by neurostructural hypothalamic plasticity in link with tanycytes retraction and by an increase of neuronal activity in the hypothalamus
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May, Aaron. "Hormonal Influence on Insulin Transport Through the Blood-Brain Barrier and Hypothalamic Inflammation". University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1479809275921804.
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Skorupskaite, Karolina. "Kisspeptin and neurokinin B in the regulation of the human hypothalamic-pituitary-gonadal axis". Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28897.
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Background: Hypothalamic kisspeptin and neurokinin B (NKB) are central regulators of GnRH and thus gonadotropin (LH and FSH) secretion. Men and women with loss-of-function mutations in NKB-kisspeptin pathway show hypogonadotropic pubertal delay with reduced GnRH/LH pulsatility. Studies in patients with defects in NKB signalling suggest that kisspeptin is functionally downstream of NKB, although there are very limited data on the relevance of the NKB pathway in normal men or women, and no hierarchical data on this. The studies described in this thesis have investigated the interaction between these neuropeptides in the control of human reproduction in conditions of varying sex-steroid environment, and in states of fast and slow LH secretion (men, menopause, various stages across the menstrual cycle). Overall hypothesis: Pharmacological blockade of NKB signalling will decrease LH secretion by modulating GnRH/LH pulsatility, indicating the involvement of the NKB pathway in normal human reproductive function. It is also hypothesised that this will not abrogate the stimulatory kisspeptin response, revealing a functional hierarchy whereby NKB signalling is upstream of kisspeptin. Research strategy: A specific neurokinin-3 receptor antagonist (NK3R antagonist, AZD4901) was administered 40 mg twice daily orally for 7 days with and without kisspeptin-10 (KP-10) challenge. Response of reproductive hormones (serum and urinary where applicable) was measured. LH was sampled every 10 minutes for 8 hours to assess LH pulsatility by blinded deconvolution. Results: Role of neurokinin B and kisspeptin in healthy men Six healthy men underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist reduced LH and testosterone secretion, whilst stimulatory LH response to KP-10 was unaffected. LH pulse frequency was unchanged by the NK3R antagonist but basal (nonpulsatile) and pulsatile LH secretion was markedly reduced. Role of neurokinin B and kisspeptin in postmenopausal women Eleven postmenopausal women underwent LH pulsatility study pre-treatment and on day 7 of NK3R antagonist administration with iv KP-10 bolus (0.3 μg/kg) at 6 hours. NK3R antagonist decreased LH secretion. Basal (nonpulsatile) LH secretion also fell and while LH pulse frequency did not change in a group as a whole, it did fall in the 8 of 11 postmenopausal womenwith hot flushes. These women reported a reduction in hot flush frequency (3.4±1.2 vs 1.0± 0.6 flushes/day with NK3Ra, p=0.008) and severity whilst on NK3R antagonist. LH response to KP-10 was minimal and unaffected by the NK3R antagonist. Role of neurokinin B across different phases of menstrual cycle The effect of NK3R antagonist on ovarian function was compared in early follicular (n=13), late follicular (n=6) and luteal phase (n=6) to no treatment control cycle. Early follicular: NK3R antagonist was commenced from cycle day 5-6. The diameter of the leading follicle was smaller than in controls at the end of treatment (9.3±0.4 vs 15.1±0.9 mm, p < 0.0001). Serum estradiol was also reduced and the endometrium was thinner. Although NK3R antagonist had no effect on LH pulse frequency, basal (nonpulsatile) LH secretion was decreased, suggesting that NKB modulates GnRH secretion. After stopping treatment, follicle development resumed and estradiol secretion increased thereby delaying the LH surge in 11/13 women (LH surge cycle day 22±1 vs 15±1, p=0.0006). The delayed LH surge and ovulation were confirmed by a similarly delayed rise in urinary progesterone and prolonged cycle length. NK3R antagonist did not affect luteal function. Late follicular: NK3R antagonist was administered from the emergence of a dominant follicle (≥12mm). Whilst there was an LH surge in all treated cycles, estrogen feedback was perturbed by the NK3R antagonist, as there was increased variation in the timing of LH surge compared to control cycle. NK3R antagonist had no effect on the growth of a dominant follicle and luteal function was unaffected. Luteal: NK3R antagonist was administered from day +2-3 of the disappearance of the dominant follicle. NK3R antagonist reduced the variation in the timing of peak estradiol secretion. Estradiol and progesterone concentrations remained unchanged, suggesting that luteal function was overall unaffected by this treatment. No difference in mean LH was observed, although LH pulsatility was not assessed. Role of neurokinin B and kisspeptin in the mid-cycle LH surge A model of follicular phase (cycle day 9-11) administration of estradiol (200μg/day) to induce LH secretion at 48 hours was used in twenty women, mimicking LH surge. In this model, KP-10 infusion (4μg/kg/hr for 7 hours) enhanced LH secretion, the response of which was directly correlated with estrogen concentration, indicating a role of kisspeptin in estrogen feedback. Pre-treatment with NK3R antagonist decreased LH pulse frequency and whilst the immediate LH response to KP-10 was unaffected, it blunted the duration of this response and abolished the relationship between estradiol and kisspeptin-induced LH secretion. Conclusions: These data indicate the role of NKB-KP pathway in regulating human reproductive function and that this is via the modulation of pulsatile GnRH secretion. Whilst NKB is predominantly proximal to kisspeptin, the hierarchy is more complex than simply linear in the control of human HPG axis. Manipulation of NKB-KP signalling has therapeutic potential in regulating GnRH/LH secretion in wide range of clinical settings, including contraception, sex-steroid dependent disorders and in the treatment of hot flushes.
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Näsman, Birgitta. "The limbic-hypothalamic-pituitary-adrenal axis in Alzheimer's disease". Doctoral thesis, Umeå universitet, Geriatrik, 1994. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140822.
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Dysfunction of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is a common finding in advanced dementia. In this study, the function of the LHPA axis at different levels was investigated in patients with dementia and in healthy elderly. A subtle disturbance in the feedback regulation of the LHPA axis was found in patients with early (i.e., mild to moderate) Alzheimer’s disease (AD). After 0.5 mg dexamethasone, serum cortisol levels were less suppressed in AD patients and plasma adrenocorticotropin (ACTH) levels were lower as compared with healthy elderly. After stimulation with human corticotropin-releasing hormone a blunted ACTH response was found in AD patients while relative serum cortisol, dehydroepiandrosterone, and androstenedione responses were increased. Significant correlations were found between low plasma ACTH levels and temporal lobe atrophy and between low peak plasma ACTH levels and hippocampal atrophy measured with computer tomography. Patients with advanced AD and multi-infarct dementia had lower basal levels of dehydroepiandrosterone sulphate in combination with no difference in cortisol levels, resulting in a high cortisol/DHAS ratio. The difference persisted after adjustments for age and sex in a multivariate analysis. In patients with early AD, basal serum levels of dehydroepiandrosterone and androstenedione were increased, and this increase was accentuated after stimulation with ACTH. Peripheral glucocorticoid sensitivity was examined by skin vasoconstrictor blanching tests. Patients with AD and patients treated with glucocorticoids showed skin blanching at higher clobetasol concentrations than healthy elderly. These findings justify further investigations on the role of LHPA axis dysfunction in Alzheimer’s disease and its possible importance for the pathophysiology of the disease.digitalisering@umu
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Kennedy, Adam Richard. "The role of melanin-concentrating hormone in the hypothalamus and the pituitary". Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.431749.
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Counsell, John R. "The role of thyroid hormone in the ventromedial nucleus of the hypothalamus". Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/9041.
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The hypothalamic arcuate and paraventricular nuclei play important roles in the neuroendocrine regulation of systemic thyroid hormone homeostasis. However, the roles of other hypothalamic regions are poorly understood. Triiodothyronine (T3) is the active form of thyroid hormone. T3 administration to the hypothalamic ventromedial nucleus (VMN) of rats stimulates feeding, although the mechanism remains unclear. Activation and inactivation of thyroid hormones is mediated by the iodothyonine deiodinases, where D2 is the activating enzyme and D3 the inactivating enzyme. Recombinant adeno-associated virus (rAAV) vectors were designed to modulate the local activity of thyroid hormones by over-expressing D2 (rAAV-D2) or D3 (rAAV-D3). Two initial investigations were carried out employing these viruses in vivo. Initially, rats received bilateral injections of either rAAV-D2 or rAAV-GFP into the VMN. Cumulative food intake and body weight were unaffected, despite a significant increase D2 enzyme activity. However, fasted rAAV-D2 treated rats consumed significantly more food than controls over the initial 2 hours of refeeding following a 12 fast. In the second investigation, rats received bilateral injections of either rAAV-D3 or rAAV-GFP into the VMN. Hypothalamic D3 mRNA and brown adipose tissue activity were both significantly increased in the rAAV-D3 group, which was not associated with any change in systemic thyroid hormone levels. This suggested that sympathetic activity had been increased, independent of peripheral thyroid status. In a final investigation, rats were challenged with a high fat diet (HFD) 17 days after iVMN injection of either rAAV-D3 or rAAV-GFP. The rAAV-D3 treated group gained significantly more weight and consumed significantly more energy than controls, per day of HFD treatment. The increased HFD consumption was matched with a significant increase in hypothalamic fatty acid synthase mRNA. This thesis highlights putative mechanisms by which thyroid hormones affect peripheral metabolism and appetite via the VMN, through interplay with neuronal fatty acid homeostasis.
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Bertherat, Jérôme. "Intéractions intrahypothalamiques entre les neurones à somatostatine et à growth hormone-releasing hormone (GHRH) dans le contrôle de l'hormone de croissance (GH) chez le rat". Paris 11, 1992. http://www.theses.fr/1992PA11T011.
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Chu, Yan-shuen Jessica. "Secretin in the rat hypothalamo-pituitary system localization, release mechanisms, and functions /". Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B31367781.
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Richy, Sébastien. "Peptides, hormones et régulation pondérale : impact des conditions nutritionnelles précoces chez le rat". Nancy 1, 2004. http://www.theses.fr/2004NAN10233.
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Ce travail se propose d'étudier l'impact de modifications nutritionnelles imposées à des femelles gestantes sur le statut peptidique et le bilan hormonal des descendants. Pendant la deuxième moitié de leur gestation, des rates sont nourries la nuit avec un régime équilibré recevant les deux tiers de leur besoin energetique. Le jour, elles ont la possibilité de compléter leur prise calorique par un régime riche en glucides (groupe G), ou en lipides (L), ou équilibré (Cr). Un autre groupe est nourri ad libitum jour et nuit avec le régime équilibré (Ca). Les ratons Cr et G naissent avec un déficit pondéral. Les rats Cr gardent toute leur vie une tendance à être plus maigres. Les animaux G parviennent à rattrapper leur déficit pondéral et montrent même une propension à l'obésité à l'âge adulte. Les rats L ne soufrent d'aucun problème de poids. Au sevrage, les animaux G surexpriment NPY et AgRP. Adultes, ces rats G présentent des taux plasmatiques élevés de glucose, d'insuline et de leptine. Malgré ces concentrations élevées, le système à NPY et AgRP du noyau arqué de l'hypothalamus n'est pas inhibé, contrairement aux neurones produisant la POMC. Ces rats possèderaient donc une resistance centrale aux hormones periphipheriquesWe studied the consequences of nutritional manipulations during gestation on hormones and peptides offsprings status. From half gestation, female rats were fed on an adequate well-balanced diet for two third of their energy needs. They were offered the possibility to complete their energy intake through the ingestion of a diet either rich in carbohydrate (HC group) or in fats (HF) or the well-balanced diet (Cr). A other group (C) was fed ad libitum on the balanced diet. At birth, HC and Cr pups were lighter than C and HF pups. At adult age, Cr rats remained lighter while HC tended to be heavier. HF animals did not have any weight problem. At weaning, NPY and AgRP mRNA expression in the arcuate nucleus was significantly higher in the HC pups. In these rats at adulthood, glucose, insulin and leptin plasma levels were increased. Despite this, NPY and AgRP hypothalamic system was not down-regulated while POMC neurons were. We concluded that a central leptin and insulin resistance could exist in these overweight HC rats
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Chautard, Thierry. "Régulation de la fonction corticotrope en période postnatale : effet des glucocorticoi͏̈des et des acides aminés excitateurs". Aix-Marseille 3, 1991. http://www.theses.fr/1991AIX30027.
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Durant les deux premieres semaines de la vie les rats presentent une reponse hypophyso-surrenalienne diminuee au stress. La suppression de la secretion ou l'action des glucocorticoides, chez des rats ages de 6 jours par surrenalectomie bilaterale ou par injection de ru 486 (un antagoniste des recepteurs aux glucocorticoides) entraine une forte elevation de l'acthemie basale. Ceci montre que pendant cette periode, les glucocorticoides exercent un retrocontrole tres marque sur la fonction corticotrope. Mais l'absence d'une augmentation supplementaire de la secretion d'acth chez ces animaux apres une exposition a des vapeurs d'ether ou une injection aigue de crf, met en evidence un deuxieme phenomene caracterise par une insuffisance de la synthese et de la secretion de crf. En effet, lorsque les rats ages de 6 jours ont ete surrenalectomises et puis traites avec du crf a action retard pendant 48 heures une reponse corticotrope au stress apparait, associee avec une augmentation du contenu hypophysaire en acth. Dans la deuxieme partie, nous avons etudie l'effet des acides amines excitateurs sur la fonction corticotrope in vivo (chez des rats de 7 jours) et in vitro (sur des antehypophyses en incubation statique et sur des cultures primaires hypothalaques). Cette stimulation intervient principalement au niveau hypothalamique sur la liberation de crf. L'ensemble des resultats montrent que les neurones a crf sont excitables durant cette periode et qu'une immaturite du systeme nerveux central incapable de transmettre la totalite du message constitue un mecanisme important a l'origine de cette periode de non-reponse au stress
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Bigeard, Lucienne. "Manifestations bucco-dento-maxillaires des insuffisances staturales d'origine hypothalamo-hypophysaire". Université Louis Pasteur (Strasbourg) (1971-2008), 1990. http://www.theses.fr/1990STR1SO01.
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Chu, Yan-shuen Jessica, i 朱恩璿. "Secretin in the rat hypothalamo-pituitary system: localization, release mechanisms, and functions". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31367781.
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Rossi, Michela. "Investigation of the role of melanin concentrating hormone and the melanocortins in the hypothalamic control of feeding". Thesis, Imperial College London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271074.
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LESLUYES, MAZZOCCHI LAURENCE. "Controle hypothalamique de la secretion d'hormone de croissance chez le belier". Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20858.
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Griffith, Ronald D. "Thyroid hormones are required during long-day photoperiods for the establishment of estradiol-sensitive afferent input to and activation of, dopaminergic neurons in the A15 area of the ovine hypothalamus". Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1580.
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Thesis (M.S.)--West Virginia University, 2000.Title from document title page. Document formatted into pages; contains viii, 46 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 33-38).
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Kelley, Jennifer Caitlin. "Effects of Estrogen and Progesterone on the Sensitivity of the Anterior Pituitary Gland and Hypothalamus in Prepubertal Rats: Role of Nitric Oxide and Dopamine". Miami University Honors Theses / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=muhonors1114785173.
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Decherf, Stéphanie. "Répression des gènes hypothalamiques Trh et Mc4r par les hormones thyroïdiennes : << de la régulation transcriptionnelle à l'intégration métabolique >>". Paris 6, 2010. http://www.theses.fr/2010PA066398.
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L’intégration centrale des signaux métaboliques est la clef de l’homéostasie corporelle. Le tissu adipeux et la thyroïde, ainsi que l’hypothalamus au niveau central sont des relais majeurs de la boucle de régulation qui contrôle la balance énergétique. L’hormone thyroïdienne (T3) est essentielle à l’établissement des niveaux de base du métabolisme. Elle régit sa propre activité en exerçant un rétrocontrôle négatif via ses récepteurs (TRs) au niveau hypothalamique, et plus précisément sur les neurones à thyrolibérine (Trh). Lors d’une augmentation des stocks adipeux, l’hormone de la satiété leptine initie une réponse neuronale au niveau de l’hypothalamus. Elle active les neurones du noyau arqué à mélanocortine (MSH) qui sécrètent alors l’MSH au niveau des noyaux paraventriculaires (PVN). Cette population de neurones, qui comprend les neurones à Trh, exprime le récepteur spécifique de l’MSH, Mc4r. La liaison de l’MSH au Mc4r stimule la synthèse et la libération de Trh, qui va activer en aval de l’axe hypothalamo-hypophyso-thyroïdien la sécrétion de T3 par la thyroïde. La leptine orchestre ainsi la régulation des signaux hypothalamiques et thyroïdiens en fonction de l’état « nourri » ou « à jeun » d’un organisme. Les travaux réalisés au cours de cette thèse ont permis de montrer que le statut thyroïdien contrôle l’expression du gène Mc4r: la T3 réprime Mc4r dans l’hypothalamus de souris (PCR quantitative & transfert de gène in vivo). Par des approches complémentaires, nous avons caractérisé le mécanisme mléculaire d’action de la T3 et des TRs au niveau du promoteur Mc4r. Un, nous avons identifié un élément de réponse fonctionnel à la T3 (TRE) dans le promoteur Mc4r (mutagenèse). Deux, nous avons montré que les récepteurs TRβ1 et TRβ2 favorisent la répression T3-dépendante du gène Mc4r (surexpression & ARN interférence). Trois, ces résultats ont été validés par immunoprécipitation de chromatine (ChIP), qui a confirmé une action directe de la T3 via les TRβ sur le promoteur Mc4r endogène. Nous avons pu également vérifier l’hypothèse que la régulation des gènes Mc4r et Trh est synergique. La T3 exerce ainsi un double rétrocontrôle sur Mc4r et Trh au niveau hypothalamique, afin de produire une réponse adaptée aux variations physiologiques du statut thyroïdien et nutritionnel de l’organisme. Ce travail est renforcé par un axe consacré à l’étude des perturbateurs endocriniens (EDCs) et leurs implications dans le dérèglement des fonctions du système hormonal et de l’équilibre énergétique. Au-delà d’effets toxiques avérés sur l’environnement, l’incidence de ces polluants sur la santé humaine est très étudiée, en particulier sur l’étiologie de l’obésité. Le retardateur de flammes tétra-bromo-bisphénol A (TBBPA) et le composé organostannique tri-butyl-étain (TBT) sont des perturbateurs potentiels de l’homéostasie thyroïdienne et métabolique. Nous avons donc étudié leur impact éventuel sur la transcription des gènes Trh et Mc4r, et observé que le TBBPA diminue l’activité basale des promoteurs Mc4r et Trh, alors que le TBT augmente celle de Trh sans affecter Mc4r. Certains polluants environnementaux peuvent ainsi modifier l’expression de gènes cibles des hormones thyroïdiennes impliqués dans la régulation centrale du métabolisme
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Kruijver, Franciscus Petrus Maria. "Sex in the brain gender differences in the human hypothalamus and adjacent areas : relationship to transsexualism, sexual orientation, sex hormone receptors and endocrine status /". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/75961.
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Allet, Cécile. "Gliogenèse dans l'hypothalamus au cours du développement postnatal : implication dans le contrôle de la maturation sexuelle femelle". Lille 2, 2006. http://www.theses.fr/2006LIL2S051.
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Notre travail propose de déterminer l'implication de la néogenèse postnatale dans la maturation des neurones hypothalamiques à GnRH, nécessaires à l'initiation de la puberté. Un nombre important de cellules prolifératives est observé dans l'hypothalamus postnatal à différents intervalles de temps après injection de BrdU. 25% des corps cellulaires à GnRH sont morphologiquement associés avec des cellules différentiées générées à P8. Par ailleurs, le nombre de ces cellules BrdU+ double entre P8 et P15. Cette vague de néogenèse précède et accompagne la première activation centrale de l'axe reproducteur. De plus, les cellules nouvellement générées se différencieraient en astrocytes plutôt qu'en neurones. Des expériences de neurosphères in vitro suggèrent la présence de cellules progénitrices multipotentes dans l'hypothalamus. Ces résultats montrent l'existence d'une néogenèse dans l'hypothalamus postnatal et suggèrent que la genèse de nouvelles cellules favorise l'initiation la pubertéThe initiation of mammalian puberty requires an increased pulsatile secretion of GnRH from specialized neurons of the hypothalamus controlling sexual development. We have identified newborn cells by injecting BrdU at various intervals thereafter. We report that during sexual maturation a host of new cells is generated in the hypothalamus. This wave of cell neogenesis precedes and accompanies the first gonadal independent GnRH-driven activation of the reproductive axis. By P15 a significant fraction of GnRH neuronal cell bodies is morphologically associated with differentiated cells that were born on P8. Moreover, upto 35% of the cells closely associated with GnRH axon terminals entering cell cycle remain associated with this neurosecretory system once differenciated. These results raise the exciting possibility that birth of new cells is a component of the maturational process required for the activation of GnRH neuronal function at the onset of puberty
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Zollner, Ekkehard Werner Arthur. "Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on corticosteroids". Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/95468.
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Thesis (PhD)-- Stellenbosch University, 2013.ENGLISH ABSTRACT: Although the effect of inhaled corticosteroids (ICS) on the hypothalamic- pituitary-adrenal axis (HPA) has been regarded as a “benign physiological response”, a survey published in 2002 suggested that adrenal crisis is more common in asthmatic children on ICS than previously thought. Relying on clinical features to detect chronic adrenal insufficiency secondary to corticosteroids may not be wise, as these are non-specific and can therefore easily be missed. Accurate biochemical assessment of the whole axis to detect subclinical HPA suppression (HPAS) is thus desirable. A review of the literature indicates that basal adrenal function tests, including plasma cortisol profiles, do not identify which children can appropriately respond to stress. There is no evidence to suggest that the degree of the physiological adjustment of the HPA to ICS and/or nasal steroids (by reducing basal cortisol production), predicts HPAS. Cortisol profiles should therefore only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Only two tests, considered as gold standard adrenal function tests [the insulin tolerance test (ITT) and the metyrapone test] can assess the integrity of the whole axis.
AFRIKAANSE OPSOMMING: Die outeurs van ´n opname wat in 2002 gepubliseer is stel voor dat ´n bynierkrisis meer algemeen by asmatiese kinders, wat inhalasie kortikosteroïede ontvang, voorkom as wat voorheen gedink is. Dit is strydig met die gevestigde opvatting dat die effek van IKS op die hipotalamiese-hipofise-bynier-as (HHB) ’n “goedaardige fisiologiese reaksie” is. Die kliniese kenmerke van kroniese bynierontoereikendheid sekondêr tot die gebruik van kortikosteroïede (KS) is nie-spesifiek en gevolglik onbetroubaar. ´n Akkurate biochemiese toets van subkliniese HBB onderdrukking (HHBO) sou gevolglik waardevol wees. ´n Literatuur oorsig toon dat toetse van basale bynierfunksie, insluitend plasma kortisol (K) profiele, nie kinders uitken wat toepaslik op stres sal reageer nie. Daar is geen bewyse dat die graad van fisiologiese aanpassing van die HHB, soos aangedui deur laer K-vlakke, na die gebruik van IKS en/of nasale steroïede (NS), HHBO voorspel nie. Serum K profiele is dus slegs van waarde om die sistemiese aktiwiteit van verskillende IKS en toedieningsstelsels te ondersoek. Slegs twee toetse, naamlik die insulien toleransie toets (ITT) en die metyrapone -(MTP)-toets (wat beide as die goue standaard van bynier funksie beskou word), kan die integriteit van die hele as meet.
Stellenbosch University
Medical Research Council
SA Thoracic Society
Harry Crossley Foundation
Red Cross Children’s Hospital.
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Jolley, Sandra. "Maternal adaptation from pregnancy to postpartum : focus on the relationship beween the hypothalamic-pituitary-adrenal axis and mood /". Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/7187.
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Armstrong, M. E. "Candidate role for nuclear hormone receptors in gene regulation in magnocellular neurones in the hypothalamus". Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596152.
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In this thesis, the expression of the unliganded, orphan receptor NGFI-B was investigated in rats which were exposed to acute- and chronic hyperosmotic stress, acute suckling and central administration of histamine. These stimuli are proven activators of OT and VP transcription in magnocellular supraoptic neurones. Using in situ hybridisation, a significant induction of NGFI-B mRNA was demonstrated in magnocellular neurones in response to acute-hyperosmotic stress and central administration of histamine, but not chronic-hyperosmotic stress or acute suckling. This may imply a differential role for NGFI-B in gene regulation in magnocellular neurones. The expression of other NHRs in the SON of acutely hyperosmotic animals was investigated using a PCR-based homology cloning strategy. This cloning strategy was based on the high degree of homology which exists within the DNA-binding domain (DBD) of all NHR superfamily members. Using degenerate primers directed against the highly conserved DBD, a number of NHRs were PCR amplified from a microdissected SON of acutely hyperosmotic rats including COUP-TFI, COUP-TFII, ERα, NGFI-B, TR4, THRα, ERR1, GCNF, COUP-gamma, Nor1 and a FTZ-F1 isoform(s). An investigation was made of the expression of the most relevant NHRs found during cloning in magnocellular neurones using in situ hybridisation. Results from these studies revealed the presence of mRNA for the orphans Nor1 and COUP-gamma in the SON of acutely hyperosmotic rats. NGFI-B and Nor1 are known to act as transcriptional activators, while COUP-gamma acts as a transcriptional repressor. Regulation of the OT and VP genes by these orphans may be mediated through the AGGTCA half-sites and DRO motif present in their promoter regions.