Dissertations / Theses on the topic 'Endocrine aspects'
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1
Ritchie, Catherine Marian. "Aspects of hypertension in endocrine disease." Thesis, Queen's University Belfast, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357488.
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Delgado, Verdugo Alberto. "Genetic Aspects of Endocrine Tumorigenesis : A Hunt for the Endocrine Neoplasia Gene." Doctoral thesis, Uppsala universitet, Endokrinkirurgi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-224111.
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Endocrine tumors arise from endocrine glands. Most endocrine tumors are benign but malignant variants exist. Several endocrine neoplasms display loss of parts of chromosome 11 or 18, produce hormones and responds poorly to conventional chemotherapeutics. The multiple endocrine neoplasia syndromes are mainly confined to endocrine tumors. This opens the question if there exists a single or several endocrine tumor genes. The aim of the study was to describe genetic derangements in endocrine tumors. Paper I: Investigation of mutational status of SDHAF2 in parathyroid tumors. SDHAF2 is located in the proximity of 11q13, a region that frequently displays loss in parathyroid tumors. We established that mutations in SDHAF2 are infrequent in parathyroid tumors. Paper II: Study of SDHAF2 gene expression in a cohort of benign pheochromocytomas (PCC) (n=40) and malignant PCC (n=10). We discovered a subset of benign PCC (28/40) and all malignant PCC (10/10) with significantly lower SDHAF2 expression. Benign PCC with low SDHAF2 expression and malignant tumors consistently expressing low levels of SDHAF2 were methylated in the promoter region. SDHAF2 expression was restored in vitro after treatment with 5- aza-2-deoxycytidine. Paper III: HumanMethylation27 array (Illumina) covering 27578 CpG sites spanning over 14495 genes were analyzed in a discovery cohort of 10 primary small neuroendocrine tumors (SI-NETs) with matched metastases. 2697 genes showed different methylation pattern between the primary tumor and its metastasis. We identified several hypermethylated genes in key regions. Unsupervised clustering of the tumors identified three distinct clusters, one with a highly malignant behavior. Paper IV: Loss of chromosome 18 is the most frequent genetic aberration in SI-NETs. DNA from SI-NETs were subjected to whole exome capture sequencing and high resolution SNP array. Genomic profiling revealed loss of chromosome 18 in 5 out of 7 SI-NETs. No tumor-specific somatic mutation on chromosome 18 was identified which suggests involvement of other mechanisms than point mutations in SI-NET tumorigenesis. Paper V: The cost for diagnostic genetic screening of common susceptibility genes in PCC is expensive and labor intensive. Three PCC from three patients with no known family history were chosen for exome capture sequencing. We identified three variants in known candidate genes. We suggest that exome-capture sequencing is a quick and cost-effective tool.
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Merani, Salima A. "Development of a specific and sensitive assay for cholecystokinin, and applications thereof." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37619.
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Cholecystokinin, or "CCK" peptides, originally identified in the gastrointestinal tract, are now considered to be one of the most abundant peptide systems in the mammalian central nervous system. Prompted by recent findings that implicated the cholecystokinergic system in the pathophysiology of various illnesses, we developed a novel assay system to measure the various forms of cholecystokinin peptides in human plasma and cerebrospinal fluid. The system detects CCK-4, sulfated CCK-8 (CCK-8s) and nonsulfated CCK-8 (CCK-8ns) with equal affinity, with the lower detection limit of 2.7 fmol and an ED50 of 10.6 +/- 2.2 fmol. Using the assay system, we determined that mean CCK-like immunoreactivity (CCK-LI) in the plasma of 12 healthy subjects was 12.9 +/- 2.1 pM CCK-4 equivalents.After developing the cholecystokinin assay system, we were able to combine our unique methodology with other established techniques to investigate the role of CCK in illnesses such as premenstrual dysphoric disorder (PMDD), anxiety, bulimia nervosa, and cardiomyopathy.
Briefly, we observed no significant differences in plasma CCK levels between women with PMDD and healthy volunteers. However, we found that, independent of diagnosis, plasma cholecystokinin concentrations were higher in women during their first visit to the clinic to participate in the study, as compared to later visits.
In addition, application of our assay system allowed us to determine that oral ingestion of caffeine increased plasma CCK-LI levels 2--4 fold in humans. Moreover, we observed substantial variation in post-caffeine cholecystokinin levels among individuals.
In another study of cholecystokinin and anxiety, we used our CCK assay to determine the effects of ondansetron, a serotonin receptor antagonist, on cholecystokinin levels in plasma. We found that multiple oral doses of ondansetron influence the pharmacokinetic parameters of exogenous CCK.
We also used the three-step assay system to measure CCK-LI in patients with the eating disorder, bulimia nervosa. Baseline fasted cholecystokinin plasma levels were lower in bulimic women as compared to control subjects. However, at "satiety", or the post-binge stage, CCK levels in bulimic women were similar to those of control women.
Finally, our investigation into the role of cholecystokinin in cardiomyopathy revealed that neuronal cholecystokinin receptor density was altered in the cardiomyopathic hamster brain, as compared to age- and sex-matched control animals. (Abstract shortened by UMI.)
4
Heaney, Anthony Patrick. "Aspects of pituitary and adrenal disease." Thesis, Queen's University Belfast, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295358.
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Henderson, Keith Meade. "Aspects of the endocrine control of ovarian function." Thesis, University of Edinburgh, 1991. http://hdl.handle.net/1842/14052.
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This thesis consists of papers, published by the candidate between 1975 and 1991, describing the results of investigations into the endocrine control of ovarian function. The papers are presented in chronological order in each of five sections. Each section deals with a different apsect of the research undertaken by the candidate during the sixteen year period. Section 2 is concerned with investigations of follicle development and follicle steroidogenesis. Papers concerned with inhibin are presented in section 3. The papers in section 4 describe studies to investigate the mechanism(s) responsible for the high ovulation rates observed in Booroola ewes carrying a fecundity (F) gene. Section 5 contains papers related to the manipulation of ovulation rate.
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Meloni, T. "SOME PERINATAL ENDOCRINE AND MORPHOLOGICAL ASPECTS OF CANINE SPECIES." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/265723.
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Despite the huge literature about dog medicine, the perinatal period of growth and development and possible perturbations of the health of fetuses and newborns are still scarcely investigated, but with a recent, increasing scientific interest. The present thesis was therefore aimed to investigate some perinatal aspects of canine perinatology. Firstly, the study focused on the presence of some growth and metabolic factors and protective substances in dog fetal fluids at term of normal pregnancy. About growth and metabolic factors, the first study showed that insulin-like growth factors I (IGF-I) were higher in amniotic (AM) than allantoic (AL) fluid and the effect of breed size, even if opposite, on both IGF-I and non-esterified fatty acids (NEFA) was evidenced. The findings suggested that AM IGF-I could be used as an indicator of growth potential in canine species, whereas AM NEFA could work as a marker of fat mobilization for an energy request. The second study on fetal fluids, aimed to assess AM and AL IgG and lysozyme concentrations, documented higher IgG levels in AM than AL fluid, as a consequence of a supposed direct fetal IgG production, whereas no significant differences were found in lysozyme values between the two fluids. Maternal parity was demonstrated to affect IgG concentrations. A second area of study was the assessment of newborns hair and nails usefulness as the newest non invasive matrices for a long-term retrospective investigation of the Hypothalamic-Pituitary-Adrenal axis activation, by cortisol (C) concentrations analysis. The study evidenced that C was detectable in both matrices, with significant higher values in premature puppies compared to term-born dead puppies or puppies dead within the first 30 days of age. Furthermore, because of the newborn puppy high susceptibility to bacterial infection, often followed by death, the fourth study investigated the bacterial involvement in canine neonatal mortality, demonstrating that bacterial infections, above all by E. coli, alone or in association with other bacteria, represent an important cause of neonatal losses. In addition, the study highlighted the importance of the antimicrobial susceptibility test in case of suspected neonatal bacterial infection for a more targeted therapy of surviving litter-mates and for a better management of further gestations in bitch with previous neonatal mortality. The last study was designed to investigate some aspects of skeletal development during the neonatal period in the attempt to provide further knowledge about the first month of skeletal growth in puppies, but also aimed to assess the possible use of some radiographic, morphometric, and anatomic parameters for the age estimation in newborn dogs. The study proved that the neonatal growth occurs gradually as the age progresses, and simultaneously in the body, limbs, and skull. The radiographic evaluation of the ossification centers appearance resulted a useful tool to estimate the neonatal age in puppies, even if during the first 14 days of age significant skeletal changes were not observed. In this respect, the radiographic and anatomic measures of the hindlimb long bones and skull length seem to provide better guarantees; specifically, the neurocranium width as well as tibial and femoral lengths resulted the most correlated measurements with the age. Thus, in the future radiographic and/or anatomical morphometry of limbs and skull could become the best tool for neonatal age estimation.
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Behera, Malabika. "Long term endocrine sequelae of childhood cancer survivors." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206611.
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Background:
Newer multimodality therapeutic interventions have resulted in dramatic survival rates in childhood cancers. However diverse treatment related morbidities affect the long term survivors. An Endocrine complication comprises 20-40% of these morbidities and affects the hypothalamic pituitary axis, growth, pubertal progression, fertility, bone health and glucose homeostasis.
Objectives:
The aim of our study was to enumerate and evaluate the frequency of endocrine complications arising as a late effect of treatment in childhood cancer survivors. Risk factors likely to be associated with these complications were also evaluated.
Methodology:
Retrospective analysis of medical records from the Long Term Endocrine Follow up clinic in the Department of Paediatrics and Adolescent Medicine of Queen Mary Hospital was done. Patients with a primary diagnosis of Cancer and Langerhans cell histiocytosis with endocrine sequelae arising from various treatment modalities who have survived 5 years after diagnosis were included in the study. Those who had endocrine complications arising from various treatment modalities for Thalassemia’s, Immunodeficiency’s were excluded from the study
Results:
135 cases were included in the study and 27 were excluded. Leukemia and Brain tumor survivors were the majority accounting for 40% and 26.67% respectively. ALL formed majority of leukemia survivors, Medulloblastoma survivors accounted for 50% of brain tumor survivors. Most common endocrine problem was Hypogonadism in 51.1% of cases, followed by growth disturbances in 40%, Thyroid dysfunction in 23% and Hyperlipidemias in 18.5%. Pubertal problems, Central Diabetes Insipidus, Adrenal insufficiency, Obesity, Altered glucose homeostasis were rest of the problems in small frequencies. PHGN (Primary Hypogonadism) was present in 91.3% and mostly in prepubertal males. PHGN was statistically associated with Leukemia survivors with OR-2.06 (1.02- 4.15), p value 0.04. The risk factors associated were exposure to alkylating agents, radiotherapy, TBI prior to transplant. SHGN (Secondary HGN) was statistically associated with Brain tumor survivor OR - 15.8 (1.7-140.5), p value 0.013. Cranial irradiation was the major risk for SHGN. PGV (Poor growth velocity) was the major growth problem.GHD (Growth Hormone Deficiency) had a highly significant association with Brain tumors (p value ˂ 0.0001), and significantly associated when all 3 modalities of treatment given together (p value 0.01). Risk factors for GHD were cranial radiotherapy, exposure to cyclophosphamide and TBI. PH (Primary Hypothyroidism) had highly significant association with craniospinal radiotherapy (p value ˂ 0.0001), and significantly associated with brain tumors. Similar results were observed in patients of CH (Central Hypothyroidism).
Hyperlipidemias were present in 18% with no statistical correlation with the type of cancer. Brain tumor survivors had a significant association of GHD, PH, CH, SHGN and CDI. Leukemia survivors had significant association with GHD and PHGN.
Conclusions:
Endocrine problems are frequent manifestations of late effects of cancer related treatments. Early detection and intervention of these potentially treatable problems could be done through structured long term surveillance. Increasing awareness among health care professionals to anticipate problems in suspected patients and education of patients would optimize health care and quality of life.published_or_final_version
Paediatrics and Adolescent Medicine
Master
Master of Medical Sciences
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Fjällskog, Marie-Louise. "Current Medical Treatment of Endocrine Pancreatic Tumors and Future Aspects." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2709.
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We treated 16 patients with somatostatin analogs combined with α-interferon and achieved a biochemical and/or radiological response in 56% (median duration 22 months). We consider this treatment a good alternative for patients who fail during chemotherapy or who do not want to/cannot receive cytotoxic drugs.
Thirty-six patients with neuroendocrine tumors were treated with cisplatin combined with etoposide. Of 14 patients with evaluable EPTs, 50% responded radiologically and/or biochemically (median duration 9 months). We consider this treatment useful as first-line medical treatment in aggressive EPTs or in patients failing prior chemotherapy.
Twenty-eight tumor tissues from EPTs were examined with immunohistochemistry regarding expression of somatostatin receptors (ssts) 1 to 5 on tumor cells and in intratumoral vessels. We found that sst2 and sst4 were highly expressed on tumor cells and in vessels. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the vessels. Because of the variability in sst expression, we recommend analysis of each individual’s receptor expression before starting treatment.
Endocrine pancreatic tumors (EPTs) are rare with an incidence of 4 per million inhabitants. In the majority of cases they grow slowly, but there are exceptions with very rapidly progressing malignant carcinomas. First-line medical treatment is streptozotocin combined with 5-fluorouracil.
We examined 38 tumor samples regarding expression of tyrosine kinase receptors platelet-derived growth factor receptors (PDGFRs), c-kit and epidermal growth factor receptor (EGFR). We found that the receptors were expressed in more than half of the tumor tissues. Further studies will reveal if tyrosin kinase antagonists can be part of the future treatment arsenal.
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Chu, Xia. "Aspects of MEN1 Tumorigenesis in Endocrine Pancreas and Adrenal Glands." Doctoral thesis, Uppsala universitet, Endokrin Onkologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-254817.
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Multiple endocrine neoplasia syndrome type 1 (MEN1) is an autosomal dominantly inherited disease, which is described as an association of tumors mainly in endocrine organs, including pancreas and adrenal glands. Pancreatic neuroendocrine tumors (PNETs) are the most common cause of death in MEN1 patients. More than one third of the MEN1 patients also develop enlargement of the adrenals. MEN1 is caused by a germline mutation of MEN1 gene, a tumor suppressor gene that is located on the human chromosome 11. As noticed, the MEN1 related tumors often develop prior to inactivation of both wild type alleles, indicating MEN1 haploinsufficiency. In this thesis, I utilized a conventional Men1 mouse model that has the phenotype mimicking the human MEN 1 traits, in order to investigate MEN1 tumorigenesis in endocrine pancreas and adrenal glands. The microvascular aberrations contributing to development and maintenance of PNETs were characterized. The increased vascular density of PNETs developed in the Men1 mice was paralleled by an early and extensive redistribution of pericytes within endocrine tissue. These morphological alterations were supported by fine-tuned variations in expression of several angiogenic regulators (VEGF, FGF and PDGF) and were further potentiated by hypoxia. Vascular reactivity and blood perfusion of tumor arterioles were significantly altered in response to glucose and L-nitro-arginine methyl ester. Investigation of adrenals from10-month-old Men1 mice showed 681 proteins in mass spectrometry data sets, in which 52 proteins were commonly found in the Men1+/+ and Men1+/- adrenals, and the differential expression between the genotypes reached significant levels. Prdx3, catalyzing the reduction of oxidative stress to cell survival, is one of the overexpressed proteins. Some proteins belonging to the PPARα pathway, e.g. ACLY were also overexpressed. Subsequent microRNA (miRNA) profiling analysis of adrenals from the same age group revealed 31 miRNAs whose expression was significantly altered in comparison between the genotypes. The tumor suppressor miRNAs, miR-486, miR-330 and miR-214, were significantly downregulated in Men1+/- adrenals. The latter, miR-214, is known to inhibit ACLY expression. This finding was in concordance with the proteomic analysis. The oncogene miRNAs, miR-132 and miR-494, were significantly enhanced in the Men1+/- adrenals. Gene ontology analysis demonstrated overrepresentation of the miRNA-targeted genes that are involved in nucleic acid metabolism, vasculature development, angiogenesis, and transcription. Together, these finding after validation in humans may be exploited to improve MEN1 cancer treatment.
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譚銓株 and Chuen-chu Tam. "Hormonal effects of the lateral prostate and seminal vesicle of the guinea pig: an ultrastructural, morphometricand cytochemical study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1989. http://hub.hku.hk/bib/B3123169X.
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Pryor, Andrew William. "Reproduction and Endocrine Aspects of Early and Mid Lactation Holstein Cows." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/32486.
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This study was designed to determine the effects of stage of lactation and subsequent energy status on metabolic and endocrine measures, follicular development, and the quality of oocytes obtained from Holstein cows. Holstein cows were selected prior to calving and assigned to the early lactation (EL) group (n=8) while, cows at d 90 postpartum were selected for the mid-lactation (ML) group (n=7). Blood samples were taken twice weekly from 4 wk prior to the start of follicular aspirations and then on through the aspiration periods for metabolite and hormone determination. Ultrasound-guided transvaginal follicular aspiration (TVFA) was conducted twice weekly for a 10-wk period on all cows. Follicular fluid samples were obtained from the largest follicle, > 10 mm in diameter, for hormone determination. All data were analyzed by ANOVA, using the general linear model procedures. Mean energy balance was positive for (2.43 ± 0.32 Mcal/kg) for ML cows and negative (-1.55 ± 0.33 Mcal/kg) for EL cows. In ML cows serum progesterone (P4) decreased rapidly from 2.7 ± 0.1 ng/ml at the first aspiration session to a nadir of 0.33 ± 0.1 ng/ml at wk 8, while follicular fluid P4 increased from 0.9 ± 0.5 to 5.6 ± 0.5 ng/ml. In the EL cows serum and follicular fluid P4 remained relatively constant over the course of aspirations. There was a linear increase in follicular fluid insulin-like growth factor I (IGF-I) for EL and ML cows, however the increase was more rapid for ML cows (159 ± 36 to 200 ± 36 ng/ml) than for EL cows (145 ± 36 to 164 ± 36 ng/ml). Over the aspiration period nonesterified fatty acids (NEFA) declined rapidly for the EL cows (0.32 ± 0.2 to 0.22 ± 0.2 mEq/L), while serum NEFA for the ML cows were relatively stable (0.19 ± 0.2 to 0.22 ± 0.2 mEq/L). The number of follicles observed during the aspiration sessions increased linearly for both EL and ML cows (P < 0.05) over the 10-wk period. However, the increase was larger for the ML cows than for the EL cows, going from 14.2 ± 0.5 to 18.1 ± 0.5 and 14.9 ± 0.3 to 15.7 ± 0.5, respectively. These results show that cows in early lactation are physiologically under more production stress than cows in mid lactation. Furthermore, increasing levels of serum and follicular fluid IGF-I in mid lactation may reflect differences in follicle and oocyte measures.Master of Science
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Rodrigues, Mark. "Hormonal and non-hormonal factors associated with cognition in post-menopausal women." University of Western Australia. School of Psychiatry and Clinical Neurosciences, 2004. http://theses.library.uwa.edu.au/adt-WU2004.0075.
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[Truncated abstract.] Alzheimer’s disease (AD) is the most common form of dementia world-wide accounting for more than two thirds of all dementia cases. AD is characterised by the presence of extracellular amyloid plaques, neurofibrillary tangles and congophillic amyloid angiopathy in the brain tissue of affected individuals. Of these neuropathological features the extracellular amyloid plaques are the most characteristic containing a peptide termed amyloid- beta (Aβ); the major protein component of these structures. In addition a number of genetic risk factors for AD have been identified. Of these the ε4 allele of the apolipoprotein E (APOE) gene found on chromosome 19 is considered to be the main genetic risk factor attributing to about 40-60% of all AD cases in most populations. Although there is strong evidence that genetic risk factors play an important role in AD they do not actually trigger the disease process. Deficits in memory and learning are the most common clinical signs of AD in the initial stages of the disease. Neuropsychological tests such as the CAMCOG and California Verbal Learning Test (CVLT) are important diagnostic tools used for the assessment of cognition. The CAMCOG is an accurate and efficient measure of global cognitive ability, while the CVLT is more specific to areas of cognition influenced in the early stages of the disease such as verbal memory. Substantial evidence indicates that changes in sex hormones following menopause in women are important factors in AD. Specifically, the reduced levels of oestrogen in post-menopausal women have been linked to cognitive decline and an increased risk of dementia. In addition the elevated level of the gonadotropins, a characteristic of the post-menopausal period, have been implicated with the disease. Numerous nonhormonal factors such as age and education may also be associated with the development and progression of cognitive decline.
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Rautio, K. (Katriina). "Effects of insulin-lowering drugs in PCOS: endocrine, metabolic and inflammatory aspects." Doctoral thesis, University of Oulu, 2006. http://urn.fi/urn:isbn:951428268X.
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Abstract
Most women with polycystic ovary syndrome (PCOS) exhibit features of metabolic syndrome, including insulin resistance, abdominal obesity, dyslipidaemia, glucose intolerance and low-grade chronic inflammation, reflected in elevated levels of serum C-reactive protein (CRP), placing these women at increased risk of cardiovascular disease and type 2 diabetes (type 2 DM).
The aim of this study was to investigate the effects of two well-known insulin-lowering drugs used in the treatment of type 2 DM, metformin and rosiglitazone, on traditional cardiovascular risk factors and inflammation in women with PCOS. In addition, the impact of rosiglitazone was evaluated as regards clinical, endocrine and metabolic aspects of PCOS.
Six-months of metformin treatment in women with PCOS had beneficial effects on levels of CRP, lipid profile and blood pressure, expressed as increased levels of high-density lipoprotein cholesterol (HDL-C), and decreased levels of triglycerides (TGs), decreased ratio of total cholesterol/HDL-C, decreased levels of CRP, and decreased systolic and diastolic blood pressures.
Four-month treatment with rosiglitazone in a randomised, double-blind, placebo-controlled study in overweight women with PCOS resulted in significant improvements in menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia. In addition, rosiglitazone decreased levels of markers of low-grade inflammation, CRP and white blood cell (WBC) count, and the liver function marker alanine aminotransferase (ALAT), while having neutral effects on levels of lipids, and blood pressure.
In conclusion, metformin treatment, in accordance with the known beneficial metabolic effects of this drug, could be useful in the prevention of cardiovascular complications in women with PCOS. Rosiglitazone represents an alternative treatment for overweight anovulatory women with PCOS. It could be useful in the prevention of type 2 DM in overweight women with PCOS and for those suffering from possible side-effects related to metformin treatment. In addition, alleviation of inflammation and improvement of liver function during rosiglitazone treatment may indicate decreased future risks of cardiovascular diseases and non-alcoholic fatty liver disease (NAFLD).
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Fridström, Margareta. "Endocrine and therapeutic aspects of infertile women with the polycystic ovary syndrome /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3175-5/.
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Teske, Sondra Sue Gery. "Aspects of Measuring Mass Balances of Endocrine Disrupting Compounds through Wastewater Treatment." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/194944.
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Ecological impacts of natural estrogens and xenoestrogens in treated wastewater include altered sexual development and sex ratios among continuously exposed organisms. The primary sources of estrogenic activity in wastewater are natural estrogens such as estrone, 17β-estradiol and estriol and synthetic compounds like 17α- ethinylestradiol, alkylphenols and alklphenol ethoxylates. Precursors in raw wastewater can yield estrogenic intermediates during wastewater treatment. All these compounds can be destroyed by biochemical processes conventional wastewater treatment processes, suggesting that conventional processes can be optimized for removal of estrogenic activity from wastewater. Sorption to sludges derived from wastewater treatment affects the fates of hydrophobic xenoestrogens such as nonylphenol, in part because the biodegradability of sorbed contaminants is limited. It may also be possible to tailor sludge stabilization processes to remove trace contaminants, including estrogens. For example, there are significant differences in the efficiencies of aerobic and anaerobic digestion for destruction of alkylphenols and probably other estrogenic compounds with aromatic moieties. Because advanced wastewater treatment is not economically feasible for most communities, there is ample incentive to develop accurate relationships between operational parameters and removal of estrogenic compounds during secondary wastewater treatment. Large quantities of polybrominated diphenyl ethers (PBDEs) have been used as flame retardants in clothing and plastic products since the 1970s. A small fraction of the PBDEs in manufactured products subsequently enters municipal wastewater. The resistance of these compounds to chemical and biochemical transformations provides opportunities for accumulation in sediments. Balances developed for PBDE congeners indicate that conventional wastewater treatment processes and soil infiltration of treated wastewater in recharge operations do not discriminate significantly among the major congeners in commercially available PBDE products. Accumulation of PBDEs at near part-per-million levels was measured in the sediments at the Sweetwater Recharge Facility in Tucson, Arizona, during 10-15 years of operation. Half times for loss of major PBDE congeners from sediments were decades or longer. Local agricultural soils amended with biosolids over a 20-year period showed similar accumulation of PBDEs. The widespread use of PBDEs in commercial products, compound persistence and toxicity indicate that additional effort is warranted to better understand fate-determining processes for PBDEs in the environment.
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Yip, Ka-yiu, and 葉嘉嬈. "Investigation of growth and endocrine disrupting effects of the mycotoxins zearalenone and aflatoxin B1 on breast cancer in vitro." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/209490.
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Despite the medical advancements, the woman breast cancer incidence rates keep rising in the past few decades. Scientists have proposed the increased exposure to endocrine disrupting chemicals as a possible factor for the rises. Zearalenone (ZEA) and aflatoxin B1 (AFB1) are common mycotoxins that are present in cereal crops worldwide. ZEA has long been recognized as a xenoestrogen, while the endocrine disrupting effects of AFB1 on steroidogenesis have been identified recently. Due to the co-occurrence and the endocrine disrupting potentials of ZEA and AFB1, the hypothesis of this project was proposed as exposure to low doses of ZEA and AFB1 might affect the growth of hormonal dependent breast cancer.
In order to address the hypothesis, the aim of the first study was to examine the ultimate effects on growth and cell cycle progression in breast cancer MCF-7 cell line, following low dose exposure to ZEA and AFB1 individually and in combination. The effects on viability, cell growth, DNA synthesis, cell cycle progression and cyclin gene expressions were determined. Significant interactions were detected for their effects on viability and DNA synthesis. While ZEA promoted growth, DNA synthesis and cell cycle progression in MCF-7 cells, AFB1 was cytotoxic and counteracted the effects of ZEA. This study confirmed the growth promoting properties of ZEA, and is the first to report the combined effects of ZEA and AFB1 on breast cancer cell growth, suggesting endocrine-disrupting mycotoxins that co-occur in human food can interact and modulate the effects of each other on human health.
The second study aimed to reveal the modulation of breast cancer genes and the underlying pathways that were directly affected by ZEA and AFB1. By using a real time reverse transcription polymerase chain reaction array, it was shown that ZEA was capable of altering the expressions of a large number of breast cancer related genes, whereas AFB1 had minimal effects on the breast cancer gene expressions. With the use of specific inhibitors, estrogen receptor α, G protein-coupled estrogen receptor 1, and mitogen-activated protein kinases (MAPKs) were found to be responsible for ZEA’s effects on cell growth and myelocytomatosis oncogene activation; while MAPK pathways might be involved in the cytotoxic effects by AFB1. Further confirmation is necessary for linking the activations of estrogen receptors and MAPKs to breast cancer cell growth by ZEA and AFB1.
The last study aimed at assessing the impacts of ZEA and AFB1 on steroidogenic and steroid metabolic enzymes in MCF-7 cells, which might result in hormonal imbalance and undesirable breast cancer cell growth. By evaluating the mRNA expressions, it was found that ZEA significantly modulated the expressions of all the steroidogenic and steroid metabolic enzymes tested while AFB1 altered the expression of cytochrome P450 (CYP) 1A1 and CYP 1B1. Coexposure of MCF-7 cells to the two mycotoxins revealed that AFB1 antagonized the effects of ZEA on expression of CYP 1A1, CYP 3A4 and CYP 1B1. Further research into the alternations of enzyme levels and activities by ZEA and AFB1 is necessary before a solid conclusion can be made.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
17
Ernestam, Sofia. "Rheumatoid arthritis : pharmacological modulation of cytokines - aspects of clinical response and endocrine regulation /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-628-X/.
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Silva, Juliana Polloni. "Aspects of endocrine disruptors remediation using in vitro and in vivo ecotoxicological assays /." Sorocaba, 2017. http://hdl.handle.net/11449/150558.
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Orientador: Renata Fracácio FranciscoResumo: Chemicals with potential to cause endocrine disruption in vertebrates and invertebrates have been detected at low concentrations in the world's aquatic environments. Therefore, the search for removal methodologies in aquatic environments became a worldwide interest. The aim of this research was to investigate three materials (powered activated carbon - PAC, powered natural zeolites - ZP and aquatic humic substances - AHS) in chemical and ecotoxicological remediation of 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) in water through chemical and biological tests in vitro and in vivo. An environmentally relevant concentration of hormones (30 ng.L-1) was used during laboratory tests. The results obtained through an extensive list of morphological, reproductive and histological parameters showed the significant impact of HSFs on the development and maintenance of exposed fish. The superior efficiency of PAC was verified in relation to the other substrates in the endocrine disrupting chemicals (EDCs) removal in water. Nevertheless, their properties did not guarantee the same performance to the environmental samples, neither allow biological injuries monitored to be recovered after the period of depuration investigated. An additional study also allowed the development of a histochemical protocol capable of identifying the production of vitellogenin (VTG) prompted by exposure to the synthetic steroid EE2.
Doutor
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Silva, Juliana Polloni [UNESP]. "Aspects of endocrine disruptors remediation using in vitro and in vivo ecotoxicological assays." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/150558.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Produtos químicos capazes de causar desregulação endócrina em vertebrados e invertebrados têm sido detectados a baixas concentrações em ambientes aquáticos do mundo. Desta maneira, tornou-se de interesse mundial a busca por metodologias de remoção mesmos nos ambientes aquáticos. Por isso pesquisa teve como objetivo investigar três materiais (carvão ativado em pós – PAC, zeólitas naturais em pó – ZP e substâncias húmicas aquáticas – AHS) na remediação química e ecotoxicológica de 17ß-estradiol (E2) e 17α-etinilestradiol (EE2) em água mediante ensaios químicos e biológicos in vitro e in vivo. Uma concentração ambientalmente relevante de hormônios (30 ng.L-1) foi utilizada durante os ensaios em laboratório. Os resultados obtidos por meio de uma extensa relação de parâmetros morfológicos, reprodutivos e histológicos adotados permitiram concluir o significativo impacto dos HSFs sobre o desenvolvimento e manutenção de peixes expostos. Comprovou-se a superior eficiência do PAC em relação aos demais substratos na remoção de interferentes endócrinos (IEs) em água. Não obstante, suas propriedades não garantiram o mesmo desempenho com relação a amostras ambientais e, tampouco possibilitou a recuperação das injurias biológicas monitoradas após período de depuração investigado. Um estudo adicional também permitiu a elaboração de um protocolo histoquímico capaz de identificar a produção de vitelogenina (VTG) incitada pela exposição ao esteróide sintético EE2.
Chemicals with potential to cause endocrine disruption in vertebrates and invertebrates have been detected at low concentrations in the world's aquatic environments. Therefore, the search for removal methodologies in aquatic environments became a worldwide interest. The aim of this research was to investigate three materials (powered activated carbon - PAC, powered natural zeolites - ZP and aquatic humic substances - AHS) in chemical and ecotoxicological remediation of 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2) in water through chemical and biological tests in vitro and in vivo. An environmentally relevant concentration of hormones (30 ng.L-1) was used during laboratory tests. The results obtained through an extensive list of morphological, reproductive and histological parameters showed the significant impact of HSFs on the development and maintenance of exposed fish. The superior efficiency of PAC was verified in relation to the other substrates in the endocrine disrupting chemicals (EDCs) removal in water. Nevertheless, their properties did not guarantee the same performance to the environmental samples, neither allow biological injuries monitored to be recovered after the period of depuration investigated. An additional study also allowed the development of a histochemical protocol capable of identifying the production of vitellogenin (VTG) prompted by exposure to the synthetic steroid EE2.
FAPESP: 2012/24495-6
FAPESP: 2014/22733-2
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Wei, Xi. "Environmental screening of endocrine-disrupting chemicals and biological characterization of their effects on reproductive health." HKBU Institutional Repository, 2011. http://repository.hkbu.edu.hk/etd_ra/1225.
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Cassidy, Carrie. "Further evidence that prostaglandin F2-alpha is the obligatory eicosanoid in porcine ovulation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0004/MQ44139.pdf.
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Melnyk, Peter M. (Peter Michael). "Estrogen regulation of testicular function in the adult ram." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59414.
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During the nonbreeding season (July), three groups of five Dorset x Leicester x Suffolk rams were assessed over a period of 5 days. One group of rams (control) was implanted (sc) with five 5cm empty Silastic capsules (i.d. 3.4mm, o.d. 4.6mm); two other groups, designated as Low-E$ sb2$ and High-E$ sb2$, received five estradiol filled capsules of either 5cm or 10cm, respectively for 4 days. Estradiol treatment elevated serum estradiol concentration about 150% in the Low-E$ sb2$ groups (15.7 $ pm$ 1.3 pg/ml) and 300% in the High-E$ sb2$ groups (26.6 $ pm$ 2.4 pg/ml) compared with controls (6.3 $ pm$ 0.8 pg/ml). In the absence of LH pulsing, mean LH, FSH and testosterone concentrations were all decreased significantly (P $<$.05) with increasing estradiol concentration, while PRL concentration was increased (P $<$.05) by as much as 105%. In the LH-pulsed groups, LH-peak height on day 4 was comparable for all three groups of rams and peak frequency was, as expected, consistently increased to 4 peaks per 6 hours. The increase in mean testosterone concentration (P $<$.05) in all three groups was due to an increase in testosterone baseline concentration and testosterone peak frequency.
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Biondi, Christine A. "Mouse models of multiple endocrine neoplasia type 1 (MEN 1)." Thesis, Queensland University of Technology, 2002.
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Krown, Kevin Alan. "Pituitary changes in force-molted hens." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185205.
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The effect of forced molt on pituitary function and other endocrine parameters was investigated in three year old hens subjected to a dietary forced molting procedure. In addition to molting, fasting caused cessation of egg production, body and organ weight loss, alterations in hormone secretion and morphological changes in some endocrine glands. Body and ovary weights decreased but returned to normal with ad libitum feeding. Pituitary, thyroid and adrenal weights were not affected but serum hormone levels measured by RIA revealed a decrease in LH, FSH and PRL and increases in TSH, T₃ and GH all of which returned to higher levels with ad libitum feeding. Serum P₄ levels remained low (and egg-laying stopped) until ad libitum feeding was resumed and then increased and egg-laying returned to a typically productive level. Serum ACTH and T₄ increased with fasting and remained elevated. Gonadotrophs and corticotrophs increased in numbers with fasting and/or food restriction but thyrotrophs, somatotrophs and lactotrophs decreased. Correlations between cell populations and serum hormone levels was quite common. Colloid-filled follicles resembling a hypertrophic thyroid gland occurred throughout the pituitary pars distalis. Granules appear to be discharged into the follicular lumen through exocytotic pores in the apical plasmalemma of follicular cells. Lactotrophs, corticotrophs and somatotrophs are commonly arranged in follicles or clusters. PRL-containing granules are in the center of some follicles and are concentrated near pituitary cysts. Pituitary cysts, lined with ciliated epithelium and sparse mucous cells, are more prevalent in fasted hens and decline with the resumption of feeding. Reduced lactotroph populations and presumptively degenerated lactotrophs in cyst lumens are correlated with reduced serum PRL levels. Necrotic cells occurred in the pituitary parenchyma of fasted birds but dilated RER in the thyrotrophs of fasted hens indicate enhanced activity of these cells. Ultrastructural evidence presented here indicates that pituitary secretion by lactotrophs occurs both intraluminally and perivascularly.
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Gevrey, Jean-Claude. "Mécanismes de réponse de la cellule endocrine intestinale aux hydrolysats protéiques : aspects sécrétoire et transcriptionnel." Lyon 1, 2002. http://www.theses.fr/2002LYO1T170.
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Walls, Gerard V. "Studies of tumourigenesis in the multiple endocrine neoplasia type 1 and hyperparathyroidism-jaw tumour syndromes." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.711626.
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Mohanty, Sanjay K. "Fate and transport of selected endocrine disrupting chemicals in recycled water through a tropical soil." Thesis, Water Resources Research Center, University of Hawaii at Manoa, 2006. http://hdl.handle.net/10125/20489.
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Hamudikuwanda, Humphrey. "Endocrine and metabolic mediators of dietary energy status and reproduction in dairy cows." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28770.
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Five experiments were undertaken to identify metabolites and hormones that could mediate the effect of dietary energy status on reproduction, particularly pulsatile secretion of luteinizing hormone (LH) postpartum dairy cows.In the first two experiments, the concentration of progesterone (P4) in tailhead adipose tissue and plasma in 12 cows at different stages of pregnancy and lactation was determined as was P4 produced in vitro by explants of tailhead adipose tissue. Concentration of P4 in adipose tissue was correlated with that of plasma P4 near estrus and during the luteal phase of the estrous cycle, and P4 was released in vitro by fat mobilization.
In the third and fourth experiments, blood was collected continuously for 16 h from four ovariectomized cows offered maintenance or restricted energy diets after priming with P4 or estradiol (E2) using a crossover experimental design. The results indicated that P4 released during body fat mobilization is minor and is not related to LH secretion. Dietary energy restriction influenced plasma LH concentration and pulse amplitude but the effect was modulated by P4 and E2 priming. Dietary energy restriction decreased glucose concentration but did not influence plasma non-esterified fatty acids (NEFA), cortisol, P4 and insulin levels. Cortisol was negatively related to LH pulse frequency. Glucose and insulin were positively and negatively correlated with LH pulse amplitude, respectively. Cortisol, NEFA and glucose jointly had a negative correlation with LH concentration.
In the fifth experiment, blood samples were collected daily for 60 d and every 10 min for 8 h on 18, 36 and 54 d postpartum from 24 cows (12 ovariectomized) fed low (1.4 Mcal/kg DM) (L) or high (1.7 Mcal/kg DM) (H) energy in a 2 x 2 factorial treatment design. LH pulse frequency was reduced at 18 d postpartum in ovariectomized cows, but not in intact cows, fed L. First postpartum ovulation occurred later in intact cows fed L compared to those fed H. Energy balance and plasma glucose concentration were lower, but plasma NEFA, $ beta$-hydroxybutyrate (BHB) and E2 concentrations higher, in cows fed L compared to those fed H. E2 concentration in intact cows fed L was elevated for a prolonged period prior to first ovulation. Diet had no influence on plasma P4 and insulin concentrations. Plasma E2 and BHB concentrations were positively correlated with LH pulse frequency in intact cows across diets and ovariectomized cows fed L, respectively. NEFA were negatively correlated with LH pulse amplitude in ovariectomized cows fed L. Glucose, NEFA and P4 were negatively, but BHB, E2 and insulin positively correlated, individually or in association, with LH concentration.
Overall, the results suggest that the effect of dietary energy status on LH patterns and timing of onset of postpartum ovulation is modulated by priming with or presence of ovarian steroids. The relationships of metabolites and hormones with LH patterns appear to change with dietary energy level, ovarian status and mutual associations among the metabolites and hormones. These parameters, especially glucose and BHB, may be potential mediators of the effect of dietary energy status on LH patterns. (Abstract shortened by UMI.)
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Cote, Fabienne. "Induction of prostaglandin endoperoxide synthase 2 in the follicles of equine chorionic gonadotropinhuman chorionic gonadotropin treated prepubertal gilts." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33741.
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Prostaglandin G/H synthase-2 (PGHS-2) is a key rate limiting enzyme in the prostaglandin (PG) biosynthetic pathway, and PG synthesis is required for ovulation in pigs. The objective of this study was to characterize the expression and regulation of PGHS-2 in porcine follicles prior to ovulation. The combination of equine chorionic gonadotropin (eCG; 750 IU) followed by human chorionic gonadotropin (hCG; 500 IU) 72 h later was used to induce ovulation in prepubertal gilts. Previous studies have shown that ovulation is generally induced between 40 and 44 h post-hCG in this model. Ovariectomies were performed at 0, 24, 30, 34 and 38 h post-hCG (n = 4 or 5 animals per time-point), and all follicles larger than 4 mm in diameter were isolated. The regulation of PGHS-1 and PGHS-2 proteins was studied by immunohistochemistry and Western blot analyses, whereas the regulation of PGHS-2 mRNA was studied by Northern blot. PG production was assessed by radioimmunoassay (RIA). (Abstract shortened by UMI.)
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Algire, James Edgar. "Prostaglandins in follicular development and ovulation in cattle." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61849.
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Ferasyi, Teuku Reza. "Mathematical model of the reproductive endocrine system in male sheep." University of Western Australia. School of Animal Biology, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0080.
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[Truncated abstract] The activity of the reproductive endocrine axis is the result of interactions among many organs and tissues, particularly the hypothalamus, pituitary gland and gonad. However, it depends on more than the communication between anatomical structures because it is also affected by genotype, internal factors (e.g., metabolic inputs) and external factors (e.g., photoperiod, socio-sexual cues, stress, nutrition). This multifactorial complexity makes it difficult to use animal experimentation to investigate the pathways and mechanisms involved. Therefore, in this study, I have turned to mathematical modelling. The general hypothesis was that, by modelling the hormonal feedback loop that links the hypothalamus, pituitary gland and gonad, I would be able to discover the critical control points in this homeostatic system. This would allow me to inform and direct research into the processes that control reproduction, including inputs from environmental factors. My studies began with the development of a model of the negative feedback loop through which testosterone controls the secretion of pulses of gonadotrophin-releasing hormone (GnRH) by the hypothalamus. The model incorporated two critical factors: testosterone concentration and a time delay in the inhibition of the activity of the GnRH 'pulse generator' by testosterone. The general assumptions were: i) there are two positive feedforward processes (GnRH pulses stimulate LH pulses, and, in turn, LH pulses stimulate testosterone secretion); ii) testosterone exerts negative feedback that reduces the frequency of GnRH pulses. The model incorporated a group of equations that represent the GnRH pulse generator, through which the inhibitory effect of testosterone acted to reduce GnRH pulse frequency. Simulations were run with various values for the time delay in feedback and, as model development progressed, the simulations were extended to include combinations of time delays and levels of sensitivity of the GnRH pulse generator to inhibition by testosterone. The output of the simulations showed clearly that a time delay in negative feedback, as well as the concentration of testosterone, can greatly affect the frequency of GnRH pulses and the shape of the GnRH secretory profile. Importantly, the effect of the time delay depends on the sensitivity of the pulse generator to testosterone. In addition, the simulations suggested two additional components that might be involved in the control of the GnRH pulse generator: i) a delay in the rate of adaptation to a change in steroid feedback; and ii) a minimum pulse interval (maximum frequency). These studies iii therefore suggest that the regulation of the activity of the GnRH pulse generator, and thus the frequency and profile of GnRH and LH pulses, requires interactions among these four components. These interactions should be tested in animal experimentation. In the next stage, I extended the model so I could test whether the feedback delay might involve the process of aromatization in which testosterone is converted to oestradiol at brain level. ... This information can be used to direct future experimental studies that will help us to understand the factors that underlie the dynamic behaviour of the hypothalamic and pituitary systems that control reproduction.
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陳展豪 and Chin-ho Chan. "Signalling pathways of M918T RET mutant in multiple endocrine neoplasia type 2B." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B34603244.
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Spaulding, Benjamin W. "Endocrine Disruption in Atlantic Salmon (Salmo salar) Exposed to Pesticides." Fogler Library, University of Maine, 2005. http://www.library.umaine.edu/theses/pdf/SpauldingBW2005.pdf.
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Guldstrand, Marie. "Endocrine aspects of obesity and weight reduction by bariatric surgery with special emphasis on beta cell function /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-631-6/.
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Zhang, Song. "Peripheral and central pathways linking metabolic status and reproduction in male sheep." University of Western Australia. School of Animal Biology, 2005. http://theses.library.uwa.edu.au/adt-WU2005.0037.
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[Truncated abstract] Reproductive activity is affected by external factors such as photoperiod, social cues, stress and nutrition, all of which can alter the pulsatile activity of the GnRH neurons, which is the major neuroendocrine system used by the brain to control gonadal function. In the male Merino sheep, nutrition is one of the most powerful factors that affect pulsatile LH secretion, used commonly to bioassay GnRH neuronal activity. More accurately, the reproductive system responds to “metabolic status”, rather than “nutrition”, and the three factors that contribute to metabolic status are food intake, the amount of body reserves and the rate of energy expenditure ... In this thesis, I tested the general hypothesis that the metabolic hormones and hypothalamic neuropeptides that are known to control food intake also mediate the effect of metabolic status on the activity of the GnRH neurons ... In conclusion, the results from my experiments provide some insight into the mechanisms by which metabolic status affects reproductive activity in male sheep. Plasma insulin, which changes with alterations in metabolic status, appears to play a critical role in the regulation of GnRH neuronal activity. The level of leptin seems to have a permissive role only in lean animals. Orexins acting via OX2 receptors could be involved in the activation of reproductive function following an acute increase in nutrition. However, the neuropeptidergic systems can not be ruled out because they might be involved in very early steps of responses to nutrition.
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Mootoo, Judy E. (Judy Elizabeth). "Lipoxygenase metabolites of arachidonic acid in the porcine ovulatory process." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22779.
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It is widely accepted that prostaglandins (PGs), produced via the cyclooxygenase pathway from arachidonic acid, are essential to the ovulatory process in the pig. In support of this, ovulation is preceded by an increase in follicular fluid (FF) PG concentration, indomethacin (INDO) suppresses both the PG increase and ovulation, and ovulation can be restored by administration of exogenous PGs (Downey and Ainsworth, 1980; Prostaglandins 19: 17-22). Recent studies in the rat have shown that ovulation is also preceded by a rise in ovarian concentrations of 15-hydroxyeicosatetraenoic acid (15-HETE), a product of the lipoxygenase pathway (Tanaka et al., 1989; Endocrinology 15: 1373-1377) and inhibition of this pathway suppresses ovulation (Reich et al., 1983; Prostaglandins 26: 1011-1020). Furthermore, INDO, a cyclooxygenase inhibitor, inhibits 15-lipoxygenase as well as PG synthesis (Tanaka et al., 1989 Endocrinology 15: 1373-1377). The PMSG/hCG prepuberal gilt model was used to investigate the involvement of 15-HETE in the procine ovulatory process, and the effect of INDO on the 15-lipoxygenase pathway. Follicular fluid concentrations of 15-HETE were elevated 40 h post hCG (p $<$ 0.01). The effects of INDO and nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase activity, on ovulation rate, FF 15-HETE and FF PGF$ rm sb{2a}$ were investigated by intraovarian administration of INDO or NDGA. INDO inhibited ovulation rate (p $<$ 0.01) and PGF$ rm sb{2a}$ (p $<$ 0.01) as well as 15-HETE (p $<$ 0.01). NDGA also suppressed ovulation rate (p $<$ 0.01) but did not inhibit 15-HETE or PGF$ rm sb{2a}$ production. In in vitro experiments, 15-HETE production by both granulosa cell (GC) and theca interna cell (TIC) cultures 40 h post hCG was greater (p $<$ 0.01) than at 0 h post hCG. INDO inhibited 15-HETE production in 40 h post hCG TIC cultures (p $<$ 0.01) but not GC cultures, while NDGA inhibited 15-HETE production by both cell types (p $<$ 0.01). These results sugges
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Grant, Gerald F. "The association between prostaglandins and the plasminogen activator/plasmin system in the porcine ovulatory process /." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=69759.
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The objectives were: (1) to determine the pre-ovulatory changes in plasminogen activator (PA) and (PA) inhibitor (PAI) activities in the porcine follicle, and, (2) to determine if changes in the PA/plasmin system associated with ovulation were prostaglandin (PG)-dependent. PA activity (change in absorbance/h/mg wet tissue weight, three gilts per treatment group) was elevated in both granulosa cells (GC) and theca interna cells (TIC) prior to human chorionic gonadotropin (hCG) administration (0.582 $ pm$ 0.171 and 0.718 $ pm$ 0.221, respectively) but returned to basal levels in these two compartments (0.023 $ pm$ 0.013 and 0.052 $ pm$ 0.024, respectively) at 29 h post-hCG. PA activity remained basal thereafter in GC but increased approximately ten-fold in the TIC (0.549 $ pm$ 0.239) at the time of ovulation (three gilts at 41 h and one of three gilts at 38 h). PAI activity did not change in TIC over the pre-ovulatory period but increased in GC as ovulation approached. PAI activity in GC peaked at 38 h (being significantly different (p $<$ 0.05) to all other times except 41 h). Although indomethacin (INDO) effectively inhibited both PG synthesis (1.1 $ pm$ 0.2 vs. 9.2 $ pm$ 0.9 ng/ml in controls) and ovulation (0 vs. 27-61% in controls), elevated PA activity (0.801 and 0.349) was detected in the TIC of two out of nine INDO-treated gilts. Levels were basal (0.074 $ pm$ 0.028) in the other gilts. These inconclusive results are believed to reflect the occurrence of ovulation earlier than predicted, in as many as 40% of control gilts, and the short duration of increased PA activity at this time. In conclusion, elevated PA activity, in GC and TIC prior to ovulation induction, may play a role in follicular development. Elevated TIC PA activity may play an important role in the ovulatory process, but is probably PG-independent.
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Kwan, Ivy. "The effect of ACTH and steroidal antiinflammatory agents on prostaglandin F2a levels in vivo and in vitro using a spontaneously established porcine granulosa cell line /." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61233.
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In vivo experiments were conducted to determine if elevated plasma glucocorticoid concentrations would suppress intrafollicular prostaglandin F2$ alpha$ (PGF2$ alpha$) synthesis and, thereby, inhibit ovulation in the pig. Following ACTH administration, PGF2$ alpha$ concentrations in FF tended to be lower than in controls. Injections of betamethasone partially suppressed the preovulatory rise of PGF2$ alpha$ in FF at 40h, although the effect was less marked than that produced by indomethacin. While no ovulations occurred in the indomethacin-treated group at any time, betamethasone resulted in a lower number of ovulated follicles at 44h than in the control animals. Progesterone concentrations were unaffected by the treatments.In vitro studies were conducted with a spontaneously established cell line developed through continuous culturing of primary granulosa cells collected from prepuberal gilts six hours after they had received PMSG. Characterization of these cells revealed that aromatase and steroidogenesis were functional but gonadotropin receptors were not present. When extracellular PGF2$ alpha$ levels were measured, dexamethasone was able to significantly suppress PGF$ sb{2 alpha}$ concentrations, but not as effectively as with indomethacin. (Abstract shortened by UMI.)
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Mahomed, Shenaaz Ismail. "Descriptive study of the oestrogenicity of run off water from small-sized industry in the Pretoria West area /." Diss., Access to E-Thesis, 2004. http://upetd.up.ac.za/thesis/available/etd-06132005-133600/.
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Höybye, Charlotte. "Endocrine and metabolic aspects of adult Prader Willi syndrome with special emphasis on the effect of growth hormone treatment /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-645-6/.
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Leung, Chun-to, and 梁鎮濤. "Cellular and molecular characterization of mammary tumor development in wild type and adiponectin deficient MMTV-PyVT mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50712640.
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Breast cancer is the most common malignant cancer in western countries. It can be classified into various types/stages according to patient age, tumor size, histological grade or hormone receptor status. Obesity is a well-known risk factor of breast tumor. Studies have shown that overweight or obese postmenopausal women have a threefold higher risk to develop breast cancer in comparison to their lean or normal counterparts. There are many mechanisms that can link obesity with breast cancer and one of the major contributors is adipokines. The main focus of this study is adiponectin. Many cellular and animal studies have illustrated the inhibitory action of adiponectin on breast cancer cell proliferation. In this study, the effect of complete loss of adiponectin expression on breast cancer development in Mouse Mammary Tumor Virus-polyomavirus middle T antigen(MMTV-PyVT)mice [PyVT(+/-)]will be investigated. Mice with [ADN(+/+)]or without [ADN(-/-)] adiponectin gene were used for comparison. It was found that PyVT(+/-)ADN(-/-)mice had earlier tumor onset time and larger tumor volume than PyVT(+/-)ADN(+/+) mice. Histological analysis has demonstrated that increased and more dispersed metastasis existed in lung tissue of PyVT(+/-)ADN(-/-)mice in comparing with PyVT(+/-)ADN(+/+)mice. The aggressiveness of adiponectin deficient tumor was preserved after implantation into immune-deficient mice. Gene expression and protein expression studies of PyVT tumor have indicated a different expression level and pattern of two important molecules: P63 and YY1.
In conclusion, tumor developed under microenvironment of adiponectin deficient will give rise to a more aggressive tumor. This tumor consistsof modified genotypes and phenotypes that are permanent and can be preserved after re-implantation into immuno-compromised mice.published_or_final_version
Pharmacology and Pharmacy
Master
Master of Medical Sciences
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Pacelli, Myra Mary. "TEMPORAL RELATIONSHIPS BETWEEN DIETARY LIPIDS AND PITUITARY RESPONSE TO EXOGENOUS GONADOTROPIN RELEASING HORMONE IN HOLSTEIN HEIFERS (LUTEINIZING, PROTECTED FAT, PROGESTERONE)." Thesis, The University of Arizona, 1985. http://hdl.handle.net/10150/275374.
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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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Schmitt, Matthias. "Endocrine and paracrine aspects of vascular control : the effects of natriuretic peptides on human capacitance in health and chronic heart failure." Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/55541/.
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The effects of natriuretic peptides on vascular control were investigated. In the major part of this thesis emphasis is placed on the effects of natriuretic peptides, in particular ANP, on regulation of regional vascular volume and venous tone in healthy volunteers (Chapter 3) and patients with chronic heart failure (Chapter 4). The second part of this thesis investigates the effects and mechanisms of action of ANP, BNP and CNP on large artery function in an ovine hind limb model (Chapter 5). Finally, the actions of the latest members of the natriuretic peptide family, namely DNP and NNP are investigated in vitro using rings of rabbit aorta in organ bath experiments (Chapter 6). The important new findings of this thesis are 1. ANP regulates regional vascular volume and venous tone over a wide range of physiological and pathophysiological plasma levels without affecting compliance. 2. Most importantly, basal ANP plasma levels contribute significantly to regulation of resting vascular tone. 3. The rank order of potency of NP in the forearm capacitance vasculature of patients with chronic heart failure is ANP BNP>CNP/Urodilatin. 4. Venous ANP responsiveness is preserved in patients with chronic heart failure despite marked impairment in the resistance vasculature. This preservation may be due to preserved venous endothelial function. 5. ANP acting locally modifies pulse wave velocity via the NPRa receptor. Neither CNP (acting via the NPRb receptor) nor cANF (acting via NPRc) elicit any immediate vasoactive effects. 6. Novel natriuretic peptide (NNP), a newly isolated NP from the venom of the green mamba snake (Dendroaspis angusepticus) has arterial vasorelaxant properties similar to those of ANP and DNP.
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Manning, Katherine L. "The influence of hormone suppression therapy and related factors on bone mineral density in cancer patients." Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1399326.
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Cancer-treatment-induced bone loss (CTBL) is a well-recognized co-morbidity that affects many cancer patients. Commonly used to treat breast and prostate cancer patients, hormone suppression therapy (HST) may accelerate bone loss, resulting in osteopenia or osteoporosis. Because of their broad clinical utility, lifestyle and dietary modifications, such as regular participation in bone-stressing exercise and calcium supplementation, are starting to play a much larger role in the prevention and treatment of CTBL. However, only limited information is available on the effects that these factors may have on bone mineral density (BMD). Purpose. The purpose of this investigation was to assess the degree of BMD change from the onset of HST to 6 months and to examine the impact that physical activity and calcium intake may have on BMD. Methods. Twelve subjects (8 females and 4 males) undergoing HST for breast or prostate cancer were enrolled in the study. BMD at the spine, dual femur, and total body was assessed by dual-energy x-ray absorptiometry at 0 and 6 months. In addition, subjects wore an accelerometer to assess physical activity level and completed a lifestyle questionnaire at baseline, 3, and 6 months after starting therapy. Aside from the 7 non-exercise subjects, 5 subjects chose to participate in The Cancer Exercise Program at Ball Memorial Hospital or complete bone-stressing exercises at home. Results. No significant changes in BMD were observed after 6 months of HST between the groups at any of the sites. When all subjects were examined together, a significant BMD decrease of 3.2% was observed at the lumbar spine. The accelerometer and lifestyle questionnaires revealed that the males were more active than the females and the exercisers were more active than the non-exercisers at both baseline and after 6 months of HST. Supplementation with calcium did not affect BMD changes at any site;although it is possible this is an effect of gender as all males were included in the same group. Lifestyle factors such as history of smoking and alcoholism were also examined, but were not correlated to changes in BMD. Conclusion. Treatment with HST results in decreases in BMD, particularly at the spine. Bone-stressing exercise helped maintain or improve total body BMD in 3 of the 5 subjects the exercise group. There appears to be no difference in BMD between those who supplemented with calcium and those who did not.School of Physical Education, Sport, and Exercise Science
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Nguyen, Tuan-Anh Thi. "Cardiovascular, metabolic, endocrine and behavioral aspects of development in postnatal lambs in relation to age, sex, lamb number and acute fluoxetine administration." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44653.
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Human newborns exposed in utero to maternally administered SSRIs such as fluoxetine (FX) have an increased risk of adverse pregnancy outcomes including poor neonatal adaptation. This comprises respiratory difficulty, jitteriness, cyanosis when feeding and persists for several days after birth. Several potential mechanisms underlying these symptoms have been proposed: 1) acute toxicity to the drugs (i.e. serotonin syndrome), 2) withdrawal syndrome due to the sudden discontinuation of maternal-fetal placental drug transfer at birth or 3) an SSRIs-elicited alteration in fetal brain development. However, the actual mechanism has not been elucidated. In addition, the safety of SSRIs for the treatment of depression in children and adolescents is uncertain. Thus, we conducted experiments in which acute i.v FX (1mg/kg) and sterile water were given to FX and control groups in the lambs at ~ 3,10 days, 1,3,6 and 12 months of age. In another cohort, daily 50mg FX was given i.v to 5 pregnant ewes via implanted catheters during late gestation (131-132d, term = 147d) for 2 weeks. Plasma FX concentrations in the newborn acute FX group were within the range measured in human infants at the same age. There was a lack of significant acute FX effects on cardiovascular-respiratory, behavioral and endocrine functions in ~ 4 day old lambs. In the lambs exposed to FX prenatally, plasma FX at birth and postnatal day (PND) 2 were low and undetectable on PND 5,10,14. However, prenatal FX-exposed lambs were hyperactive during PND 4 to 14 and their heart rate variability (HRV) was significantly lower than control lambs on PND 2. Results suggested that SSRI toxicity and withdrawal are unlikely to be the mechanism underlying poor neonatal adaptation in human exposed to FX in utero. However, acute FX effects were seen in some, but not all, age groups. No acute FX effects were observed in the young lambs (10d and 3 months of age). However, hypoactivity, transient hypoxemia, hypertension and increased HRV occurred after acute FX administration in the older lambs (1,6 and 12 months of age). Hypoxemia and hypertension effects were more profound in males. No changes in HPA axis function were observed
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Xu, Genbo, and 徐亘博. "An integrated environmental risk assessment for marine protected areas in Hong Kong with special reference to the ecological impacts of endocrine disrupting chemicals." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208575.
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Johnson, Mark Steven 1955. "EFFECTS OF ELEVATING BLOOD LIPIDS IN ENERGY DEFICIENT ANESTROUS DAIRY HEIFERS ON PITUITARY RESPONSE TO GONADOTROPIN RELEASING HORMONE CHALLENGE." Thesis, The University of Arizona, 1985. http://hdl.handle.net/10150/275384.
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Gomes, D. G. Thushari Sandamali [Verfasser], and Ludwig [Akademischer Betreuer] Gortner. "Intrauterine Growth Retardation Among Preterms In Sri Lanka : Clinical, Endocrine and Molecular Aspects of Folate Metabolism / D.G. Thushari Sandamali Gomes ; Betreuer: Ludwig Gortner." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2009. http://d-nb.info/1174589787/34.
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Fernandes, Herman A. "Vitellogenesis in the teleost Brachydanio rerio (Zebra fish) /." Title page, abstract and table of contents only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phF363.pdf.
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