Relevant bibliographies by topics / Pregnenolone

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Academic literature on the topic 'Pregnenolone'

Author: Grafiati
Published: 4 June 2021
Last updated: 19 February 2022

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Journal articles on the topic "Pregnenolone"

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McKay, S. A., G. Jenkin, and G. D. Thorburn. "Peripheral plasma concentrations of pregnenolone sulphate, pregnenolone, progesterone and 20α-hydroxy-4-pregnen-3-one in ewes throughout the oestrous cycle." Journal of Endocrinology 113, no. 2 (May 1987): 231–37. http://dx.doi.org/10.1677/joe.0.1130231.

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ABSTRACT Pregnenolone sulphate, pregnenolone, progesterone and 20α-hydroxy-4-pregnen-3-one concentrations in peripheral plasma of normal cyclic ewes were measured by radioimmunoassay. The concentrations of these steroids were correlated with that of progesterone. The concentrations of all the steroids measured in peripheral plasma varied in a cyclic manner and showed a significant (P <0·05) positive correlation with the concentration of progesterone. Peripheral plasma concentrations of these steroids in ovariectomized and ovariectomized, dexamethasone-treated ewes were also determined. The plasma concentration of progesterone in ovariectomized ewes was undetectable but the concentrations of pregnenolone sulphate, pregnenolone and 20α-hydroxy-4-pregnen-3-one remained similar to those observed at oestrus. Administration of dexamethasone to ovariectomized ewes had no effect on pregnenolone sulphate or pregnenolone concentrations but 20α-hydroxy-4-pregnen-3-one concentrations, which were already very low, decreased further. It is proposed that the ovary, probably the corpus luteum, secretes pregnenolone sulphate, pregnenolone and 20α-hydroxy-4-pregnen-3-one; however, pregnenolone sulphate and 20α-hydroxy-4-pregnen-3-one may also arise from the metabolism of circulating pregnenolone and progesterone. J. Endocr. (1987) 113, 231–237.
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Tsang, Benjamin K., David F. Mattice, Ming Li, and Elikplimi K. Asem. "Effect of calcium ionophore A23187 on pregnenolone metabolism to progesterone in rat granulosa cells." Canadian Journal of Physiology and Pharmacology 66, no. 7 (July 1, 1988): 960–63. http://dx.doi.org/10.1139/y88-157.

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The effect of calcium ionophore A23187 on the metabolism of pregnenolone to progesterone was examined in rat granulosa cells during a 24-h culture period. Granulosa cells harvested from pregnant mare's serum gonadotropin treated immature rats were incubated in the presence and absence of the divalent cation ionophore A23187. The ionophore induced progesterone synthesis from both endogenous sterol substrate and exogenous pregnenolone in a time- and concentration-dependent manner. Pregnenolone metabolism was examined in the presence of aminoglutethimide phosphate, an inhibitor of endogenous pregnenolone production. Steroid secretion resulting from metabolism of endogenous substrate was more sensitive to A23187 in that a lower concentration of the ionophore was required to induce a significant increase than that noted for exogenous pregnenolone metabolism. In addition, progesterone production from endogenous sterol occurred 6 h earlier than the observed increase in the conversion of pregnenolone to progesterone. These results indicate that A23187 and therefore possibly enhanced calcium influx may play a significant role in the regulation of pregnenolone metabolism in granulosa cells depending on the duration of incubation. The earlier steroidogenic response from endogenous substrate may be a reflection of an acute effect of A23187 on certain steroidogenic steps proximal to pregnenolone production.
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Tian, Yuan, Yang Hong, Samuel J. Bonacorsi, Aaron Balog, and Sharon Gong. "Synthesis of [3α-3H] 17α-Hydroxy pregnenolone and [3α-3H] Pregnenolone." Journal of Labelled Compounds and Radiopharmaceuticals 57, no. 1 (October 24, 2013): 1–11. http://dx.doi.org/10.1002/jlcr.3114.

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Jiang, Jingjing, Xue Liu, Xiaotian Liu, Zhongyan Tian, Haiqing Zhang, Xinling Qian, Zhicheng Luo, et al. "The effect of progesterone and pregnenolone on diabetes status in Chinese rural population: a dose–response analysis from Henan Rural Cohort." European Journal of Endocrinology 181, no. 6 (December 2019): 603–14. http://dx.doi.org/10.1530/eje-19-0352.

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Objective Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case–control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose–response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population. Design A case-control study. Methods A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone. Results Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99–3.55)) and T2DM (OR (95% CI): 6.41 (4.57–8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16–0.33)) and T2DM (OR (95% CI): 0.44 (0.31–0.62)). Additionally, the nonlinear dose–response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis. Conclusions Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose–response manner in Chinese rural population.
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Legacki, Erin L., Barry A. Ball, C. Jo Corbin, Shavahn C. Loux, Kirsten E. Scoggin, Scott D. Stanley, and Alan J. Conley. "Equine fetal adrenal, gonadal and placental steroidogenesis." Reproduction 154, no. 4 (October 2017): 445–54. http://dx.doi.org/10.1530/rep-17-0239.

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Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data.CYP17A1was higher in fetal gonads than adrenals or allantochorion, andHSD3B1was higher in fetal adrenals and allantochorion than gonads.CYP11A1transcript was also significantly higher in adrenals and gonads than allantochorion andCYP19and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. LowCYP11A1but highHSD3B1andSRD5A1transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion.
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Costa, Barbara, Stefano Pini, Pamela Gabelloni, Eleonora Da Pozzo, Marianna Abelli, Lisa Lari, Matteo Preve, Antonio Lucacchini, Giovanni B. Cassano, and Claudia Martini. "The Spontaneous Ala147Thr Amino Acid Substitution within the Translocator Protein Influences Pregnenolone Production in Lymphomonocytes of Healthy Individuals." Endocrinology 150, no. 12 (October 21, 2009): 5438–45. http://dx.doi.org/10.1210/en.2009-0752.

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Abstract The de novo production of steroids and neurosteroids begins in mitochondria by the conversion of cholesterol to pregnenolone through cytochrome P450 side-chain cleavage (CYP11A1) enzymatic activity. The C-terminal amino acid domain of the translocator protein (TSPO) has been demonstrated to bind cholesterol, thereby determining its mitochondrial translocation. The goal of the present study was to investigate the effect of the Ala147Thr single-nucleotide polymorphism localized in this TSPO region on pregnenolone production in healthy volunteers. Pregnenolone production was evaluated in a peripheral cell model, represented by circulating lymphomonocytes. First, CYP11A1 expression, both at mRNA and protein level, was demonstrated. Pregnenolone production varied among genotype groups. Comparison of pregnenolone mean values revealed that Thr147 homozygous or heterozygous individuals had significantly lower pregnenolone levels compared with Ala147 homozygous individuals. These findings suggested a dominant effect of the minor allelic variant Thr147 to produce this first metabolite of the steroidogenesis pathway. Interestingly, Ala147 homozygous individuals exhibited significant higher levels of circulating cholesterol-rich low-density lipoproteins with respect to heterozygous individuals. In conclusion, our results demonstrate that the Ala147Thr spontaneous amino acid substitution within TSPO is able to affect pregnenolone production; this should encourage further studies to investigate its potential role in polygenic dyslipidemias.
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Vallée, Monique, Sergio Vitiello, Luigi Bellocchio, Etienne Hébert-Chatelain, Stéphanie Monlezun, Elena Martin-Garcia, Fernando Kasanetz, et al. "Pregnenolone Can Protect the Brain from Cannabis Intoxication." Science 343, no. 6166 (January 2, 2014): 94–98. http://dx.doi.org/10.1126/science.1243985.

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Pregnenolone is considered the inactive precursor of all steroid hormones, and its potential functional effects have been largely uninvestigated. The administration of the main active principle of Cannabis sativa (marijuana), ∆9-tetrahydrocannabinol (THC), substantially increases the synthesis of pregnenolone in the brain via activation of the type-1 cannabinoid (CB1) receptor. Pregnenolone then, acting as a signaling-specific inhibitor of the CB1 receptor, reduces several effects of THC. This negative feedback mediated by pregnenolone reveals a previously unknown paracrine/autocrine loop protecting the brain from CB1 receptor overactivation that could open an unforeseen approach for the treatment of cannabis intoxication and addiction.
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French, Joseph T., and Thomas H. Welsh. "In vitro modulation of porcine Leydig cell steroidogenesis by phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol." Acta Endocrinologica 122, no. 1 (January 1990): 101–6. http://dx.doi.org/10.1530/acta.0.1220101.

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Abstract Serum-free primary cultures of neonatal (1-day-old) porcine Leydig cells were used to study the effects of phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol on testosterone and pregnenolone production. Phorbol-12-myristate-13-acetate alone from 0.001-10 μmol/l stimulated testosterone and pregnenolone production, whereas 1,2-dioctanoylglycerol alone had no effect on steroid production, relative to control. Phorbol12-myristate-13-acetate and 1,2-dioctanoylglycerol each inhibited pLH-stimulated testosterone and pregnenolone production. To further clarify the influence of these protein kinase C activators on steroidogenesis, cultured Leydig cells were treated with either phorbol-12-myristate-13-acetate or 1,2-dioctanoylglycerol plus forskolin (an adenylate cyclase activator). Both phorbol-12-myristate-13-acetate and 1,2-dioctanoylglycerol inhibited forskolin-stimulated testosterone production. Phorbol-12-myristate-13-acetate had no effect on forskolin-stimulated pregnenolone production and only the highest concentration of 1,2-dioctanoylglycerol (100 μmol/l) inhibited forskolin-stimulated production of pregnenolone. These data demonstrate that porcine Leydig cell steroidogenesis can be modulated by interactions of the protein kinase C and protein kinase A second messenger systems.
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Mayer, Sabine I., Isabelle Müller, Stefanie Mannebach, Takeshi Endo, and Gerald Thiel. "Signal Transduction of Pregnenolone Sulfate in Insulinoma Cells." Journal of Biological Chemistry 286, no. 12 (January 21, 2011): 10084–96. http://dx.doi.org/10.1074/jbc.m110.202697.

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The neurosteroid pregnenolone sulfate acts on the nervous system by modifying neurotransmission and receptor functions, thus influencing synaptic strength, neuronal survival, and neurogenesis. Here we show that pregnenolone sulfate induces a signaling cascade in insulinoma cells leading to enhanced expression of the zinc finger transcription factor Egr-1 and Egr-1-responsive target genes. Pharmacological and genetic experiments revealed that influx of Ca2+ ions via transient receptor potential M3 and voltage-gated Ca2+ channels, elevation of the cytosolic Ca2+ level, and activation of ERK are essential for connecting pregnenolone sulfate stimulation with enhanced Egr-1 biosynthesis. Expression of a dominant-negative mutant of Elk-1, a key regulator of gene transcription driven by a serum response element, attenuated Egr-1 expression following stimulation, indicating that Elk-1 or related ternary complex factors connect the transcription of the Egr-1 gene with the pregnenolone sulfate-induced intracellular signaling cascade elicited by the initial influx of Ca2+. The newly synthesized Egr-1 was biologically active and bound under physiological conditions to the regulatory regions of the Pdx-1, Synapsin I, and Chromogranin B genes. Pdx-1 is a major regulator of insulin gene transcription. Accordingly, elevated insulin promoter activity and increased mRNA levels of insulin could be detected in pregnenolone sulfate-stimulated insulinoma cells. Likewise, the biosynthesis of synapsin I, a synaptic vesicle protein that is found at secretory granules in insulinoma cells, was stimulated in pregnenolone sulfate-treated INS-1 cells. Together, these data show that pregnenolone sulfate induces a signaling cascade in insulinoma cells that is very similar to the signaling cascade induced by glucose in β-cells.
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Lambert, F., J. Lammerant, and J. Kolanowski. "The mechanism of the prolonged stimulatory effect of corticotrophin on pregnenolone production by guinea-pig adrenocortical mitochondria." Journal of Endocrinology 108, no. 3 (March 1986): 377–84. http://dx.doi.org/10.1677/joe.0.1080377.

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ABSTRACT The postulated prolonged stimulatory influence of ACTH on the adrenocortical mitochondrial synthesis of pregnenolone in response to ACTH was studied in adrenal mitochondria isolated from control guinea-pigs and from animals treated s.c. with 100 μg ACTH(1–24) twice daily on the day before the animals were killed. The animals from both groups were injected with 100 μg ACTH s.c. 30 min before killing. The mitochondrial production of pregnenolone (expressed in nmol per mg mitochondrial protein after 10-min incubation) increased from 1·52 ± 0·46 (s.e.m.) in the control group to 4·50 ± 0·59 for mitochondria from ACTH-treated animals, despite a similar free cholesterol content in the mitochondria, even when determined after a previous in-vivo treatment with aminoglutethimide to block further metabolism of cholesterol into pregnenolone. In addition, in the presence of an excess of exogenous cholesterol (100 μmol/l), the production of pregnenolone remained higher for mitochondria from ACTH-treated animals. In contrast, when the calcium concentration in the incubation medium was raised to 1 mmol/l, with subsequent enhancement in pregnenolone synthesis, the mitochondrial pregnenolone production became similar for both groups (8·28 ± 1·11 nmol in the ACTH-treated group and 9·55 ± 1·90 nmol in the control group), even in the presence of 100 μmol cholesterol/l (13·5 ±1·80 nmol in ACTH-treated animals and 14·8 ± 1·93 nmol in controls). Cycloheximide treatment administered on the day before the animals were killed was without any effect on pregnenolone production in control animals (3·51 ± 0·43 nmol before and 3·65 ± 0·63 nmol after cycloheximide treatment). In contrast, the pregnenolone production by mitochondria from ACTH-treated guinea-pigs injected with cycloheximide was reduced to a level similar to that observed in the control group (5·82± 0·23 nmol in the absence and 3·09± 0·32nmol in the presence of cycloheximide treatment). The results of the present study suggest that the prolonged stimulatory effect of ACTH on pregnenolone production involves an increase in the synthesis of a protein factor which promotes the availability of cholesterol to the side-chain cleavage system. Other mechanisms such as a stimulated synthesis of the side-chain cleavage complex itself or an increased total mitochondrial cholesterol content are not supported by our data. J. Endocr. (1986) 108, 377–384
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Dissertations / Theses on the topic "Pregnenolone"

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Sowa, Calan B. "The role of pregnenolone sulfate in modulating neuronal excitability." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12230.

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Thesis (M.A.)--Boston University
The central nervous system operates through a tightly balanced relationship of excitatory and inhibitory synaptic transmission. Neurosteroids, synthesized de novo from cholesterol in the human brain as well as converted from precursors circulating in the blood, are proven modulators of this synaptic activity. Pregnenolone sulfate, one of the most abundant endogenous neurosteroids, is a negative modulator of the GABA receptor and positive modulator of NMDA and AMPA receptors, increasing the frequency of excitatory transmission in the brain. Here, we show that low concentrations (50pM) of pregnenolone sulfate increase receptor trafficking in cultured rat hippocampal and cortical cells. Immunocytochemistry data shows that a ten-minute treatment with 50pM PS increases NR2B subunit protein. Preliminary surface biotinylation results highlight a potential increase in NR1 subunit protein. Since NMDA receptors play a pivotal role in learning and memory and have been implicated in neuropsychiatric disorder, an endogenous positive modulator of NMDA receptors is likely to play a major pharmaceutical role in neurodegenerative and memory disorders.
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Darnaudéry, Muriel. "Sulfate de pregnenolone et mémoire : aspects comportementaux, neurochimiques et électroencéphalographiques." Bordeaux 2, 1998. http://www.theses.fr/1998BOR28608.

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Sano(Hamasaki), Mayumi. "Pregnenoloneは分裂期のcentriole engagementを制御する." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/195989.

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HU, ZHONG YI. "Neurosteroides : biosynthese et metabolisme de la pregnenolone dans les oligodendrocytes du cerveau de rat." Paris 6, 1989. http://www.theses.fr/1989PA066248.

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Les mitochondries d'oligodendrocytes de rats ages de 3 semaines transforment le #3h-cholesterol en #3h-pregnenolone(p), en #3h-pregn-5-ene-3 beta, 20 alpha-diol (20-oh-p). Les cultures primaires de cellules gliales de rats nouveaux-nes contiennent 60% d'oligodendrocytes, comme indique par la detection immunocytochimique au galactocerebroside, les oligodendrocytes contiennent aussi un antigene reconnu par des igg anti-p450scc, ces cultures primaires convertissent le #3h-mevolonolactone (mva) en #3h-cholesterol(c), en #3h-p et en #3h-20-oh-p. Les oligodendrocytes subissent un processus de differenciation en culture comme l'indique en l'occurence l'augmentation de la phosphohydrolase de nucleotide 2,3-cyclique et l'activite steroidogenique. L'aminoglutethimide empeche la formation des hormones steroides, le #3h-c s'accumule dans les cellules, une fois les cellules transferees dans un milieu sans #3h-mva et sans aminoglutethimide, elles produisent de la #3h-20-oh-p. La production des steroides est stimulee par le camp et par le dexamethasone. La #3h-pregnenolone formee est ensuite convertie en hormone steroide: la #3h-progesterone et en #3h-3 alpha-hydroxy-5 alpha-pregnane-20-one, un steroide anesthesique. Les resultats obtenus permettent de definir la biosynthese des neurosteroides comme une nouvelle fonction du cerveau, leur role physiologique fera l'objet de recherches ulterieures
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Tomaselli, Giovanni. "Role of pregnenolone derivative AEF0117 on the regulation of CB1 signaling that mediates behavioral effects of THC." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0122.

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Le cannabis sativa est l'une des drogues les plus consommées dans le monde. Le THC, sa principale composante psychoactive, représente un facteur de risque de pathologies mentales, telles que le trouble de la consommation de cannabis, la dépendance et la psychose. Le THC a un effet biphasique, de fortes doses de THC provoquent une hypoactivité et une aversion, tandis que de faibles doses de THC provoquent une hyperactivité et une récompense. Le THC agit sur le récepteur aux cannabinoïdes de type 1 (CB1), dont la signalisation est biaisée avec différents transducteurs pouvant véhiculer une voie spécifique selon différentes conditions. Il a été prouvé que la signalisation biaisée est pertinente dans la découverte de médicaments et la compréhension de la signalisation CB1 est essentielle pour le développement de médicaments à base de cannabinoïdes. Même si il a été montré que différentes doses de THC entraînent des effets comportementaux, cellulaires et moléculaires différents, le lien entre ces phénomènes n'a jamais été étudié.En outre, il a été découvert que la pregnénolone (PREG) est un modulateur allostérique endogène biaisé du CB1, en étant un inhibiteur de signalisation spécifique du récepteur CB1 (CB1-SSi) et capable de bloquer des comportements induits par le THC. Comme la PREG est un précurseur de stéroïde, son administration à forte dose peut induire la production de stéroïdes, avec d'éventuels effets secondaires.Ainsi, dans un but thérapeutique, des composés CB1-SSi analogues à la PREG ont été synthétisés, ayant le même potentiel thérapeutique que la PREG, mais sans être métabolisés en stéroïdes. Le CB1-SSi étudié ici est le composé CB1-SSi leader, l’AEF0117.Le premier objectif de ce travail était de comprendre les voies de signalisation intracellulaires selon des doses faibles, moyennes et élevées de THC, conduisant à respectivement l'hyperlocomotion, l'asociabilité et l'hypolocomotion chez la souris.Le second objectif était de comprendre le mécanisme d'action de l’AEF0117 et sa capacité à bloquer les effets comportementaux et moléculaires du THC à faibles, moyennes et fortes doses.La thèse est divisée en cinq parties. L'introduction sert à préfacer les concepts du système endocannabinoïde, ainsi que l'abus de cannabis chez l'homme et les effets comportementaux du THC chez la souris, comme l'hyperlocomotion, l'asociabilité et l'hypolocomotion. L'état de l'art de la signalisation CB1 impliquant le système CB1 biaisé est décrit avec un accent particulier sur les inhibiteurs spécifiques de la signalisation CB1 (CB1-SSi), en particulier la pregnénolone endogène (PREG), et son analogue synthétique, l’AEF0117.L'article Zanese*, Tomaselli* et al, 2020 (publié dans J. Neurosci. Methods) porte sur la validation de la technique analytique à haut débit (AlphaLISA) de choix dans cette étude pour la détection de la phosphorylation des protéines dans les lysats de tissu cérébral.L'article de Tomaselli et al. (à soumettre) est consacré à l'étude de faible dose de THC qui provoque l'hyperlocomotion chez la souris. Les principales données ont révélé que le THC via CB1 recrute la voie de signalisation β-Arrestin1-PI3K-Akt-GSK3β, dans les zones du cerveau riches en CB1 et pertinentes pour l'activité locomotrice (NAc, Str, CB), qui conduit à l'hyperlocomotion. En outre, PREG et AEF0117 peuvent bloquer l'hyperlocomotion et les modifications de la signalisation CB1 induite par le THC.La troisième partie représente les études sur les effets du THC à des doses moyennes et élevées qui induisent respectivement un comportement asocial et une hypolocomotion. Chaque dose de THC induit des altérations spécifiques des voies de signalisation intracellulaires CB1 et le traitement avec l’AEF0117 réverse les deux comportements.La discussion générale aborde ensuite le rôle des voies CB1 spécifiques dans la dépendance et la psychose induites par le THC, et propose un mécanisme d'action pour les composés CB1-SSi, dont l’AEF0117
Cannabis sativa is among the most abused drugs worldwide. THC, its main psychoactive component, represents a risk factor of several mental pathologies, such as cannabis use disorder, addiction, and psychosis. Being a biphasic drug, high doses of THC cause hypoactivity and aversion, whereas low doses of THC cause hyperactivity and reward. THC acts on the type-1 cannabinoid receptor (CB1), one of the most abundant G-protein coupled-receptors (GPCRs) in the brain, whose signaling is biased, meaning that different transducers can carry specific pathway following different conditions. Biased signaling was proven to be extremely relevant in drug discovery and understanding CB1 signaling in pathologic conditions is essential for cannabinoid-based drug development. It is known that different doses of THC bring along different behavioral, cellular, and molecular outcomes. However, the link between those phenomena has never been investigated.Thus, for a therapeutic purpose PREG-like CB1-SSi compounds have been synthetized that share the same PREG therapeutic potential, but cannot be metabolized in downstream steroids. The CB1-SSi studied in the current work is the CB1-SSi lead compound, AEF0117.The first aim of the current work was to understand the intracellular signaling pathways following low, medium, and high doses of THC, leading to three distinct known behavioral outputs in mice, hyperlocomotion, asociability, and hypolocomotion, respectively.The second aim of the thesis was to understand the mechanism of action of AEF0117, and its capability to block the behavioral and molecular effects of THC at low, medium, and high doses.The doctoral dissertation is divided into five main parts. The introduction serves to preface the concepts of the endocannabinoid system, as well as cannabis abuse in humans and the counterpart behavioral outcomes of THC in mice, including hyperlocomotion, asociability, and hypolocomotion. The state of the art of CB1 signaling involving the biased CB1 system is described with particular emphasis on CB1 Signaling Specific Inhibitors (CB1-SSi), in particular the endogenous pregnenolone (PREG), and its synthetic analogue, the lead CB1-SSi compound, AEF0117.The article Zanese*, Tomaselli* et al., 2020 (published in J. Neurosci. Methods) oversees the validation of the high throughput analytical technique (AlphaLISA) of choice in this study for detection of protein phosphorylation in brain tissue lysates.The article Tomaselli et al. (to be submitted), is devoted to the studies of the low dose of THC that causes hyperlocomotion, with the discovering of its related intracellular CB1 signaling pathway, along with the signaling transducer involved in the CB1-rich brain areas relevant for locomotor activity (NAc, Str, CB). The main data revealed that THC via CB1 recruits the β-Arrestin1-PI3K-Akt-GSK3β signaling pathway that lead to hyperlocomotion. Furthermore, both PREG and AEF0117 were able to block the THC-induced hyperlocomotion and altered signaling in mice.The third part of the data represent studies on the effects of THC at medium and high doses that induce asocial behavior and hypolocomotion, respectively. Each dose of THC induced specific alterations in the CB1intracellular signaling pathways in the most CB1-rich brain areas, and the treatment with AEF0117 rescued both behaviors.The general discussion then addresses conclusions and perspectives, highlighting the role of specific CB1 pathways in THC-induced addiction and psychosis, and proposes a mechanism of action for CB1-SSi compounds, including AEF0117
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Cox, Michele Margaret Freedman William McElligott James G. "The effects of a neurosteroid, pregnenolone sulfate, in the cerebellum on vestibulo-ocular reflex adaptation (VOR) in goldfish /." Philadelphia, Pa. : Drexel University, 2006. http://hdl.handle.net/1860/1119.

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Whang, Daniel. "Regulation of 7 alpha-hydroxylation of dehydroepiandrosterone and pregnenolone in human adipose stromal cells, mechanistic and expression studies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq30833.pdf.

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Urs, Aarti N. "Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17." Thesis, Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-11212005-102620/.

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Thesis (M. S.)--Biology, Georgia Institute of Technology, 2006.
Donald Doyle, Committee Member ; Harish Radhakrishna, Committee Member ; Alfred Merrill, Committee Member ; Marion Sewer, Committee Chair Includes bibliographical references.
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Young, Jacques. "Les neurosteroides chez le rat et la souris : correlations fonctionnelles." Paris 11, 1996. http://www.theses.fr/1996PA11T006.

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Rouiller-Fabre, Virginie. "Production de pregnenolone et de progesterone par l'ovaire foetal de rat in vitro : ontogenese et regulation des activites enzymatiques." Paris 6, 1989. http://www.theses.fr/1989PA066436.

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Classiquement, il est admis depuis de nombreuses annees que l'ovaire ftal de mammifere ne possede pas d'activite staroidogene alors que, au meme moment, chez le male, une synthese de testosterone apparait. Le but de notre travail a ete de rechercher chez le rat les etapes limitantes de la steroidogenese ovarienne, au cours de la vie ftale. Nous avons etudie les deux etapes conduisant a la production de progesterone. Dans une premiere serie d'experiences, nous avons suivi, par dosage radioimmunologique, la production de pregnenolone et de progesterone d'ovaires ftaux de 18,5 j. P. C. Explantes soit en milieu temoin, soit en presence de dibutyryl ampc (dbampc). Dans une seconde approche experimentale, nous avons evalue l'activite 3-hydroxysteroide deshydrogenase (3-hsd) en mesurant la conversion de pregnenolone #3h en progesterone #3h dabs des homogenats d'ovaires de 18,5 j. P. C. Cette activite est presente dans l'ovaire ftal. De la meme facon, l'activite de clivage de la chaine laterale du cholesterol (activite scc) a ete evaluee dans les mitochondries isolees en mesurant la conversion du cholesterol #3h en pregnenolone #3h. Absente au niveau des ovaires ftaux, cette activite peut etre induite par un pretraitement avec le dbampc. Enfin, l'analyse en immunoblotting nous a permis de mettre en evidence la presence du cytochrome p-450scc (composant du complexe enzymatique de clivage) dans les ovaires ftaux pretraites par le nucleotide, alors qu'il est absent dans les ovaires temoins. En conclusion, la premiere etape de la steroidogenese est une etape limitante pour l'ovaire ftal de rat. Cette etape peut etre induite par le dbampc
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Books on the topic "Pregnenolone"

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Pregnenolone: Nature's feel good hormone. Garden City Park, N.Y: Avery Pub. Group, 1997.

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Dolby, Victoria. Pregnenolone. McGraw-Hill, 1999.

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Pregnenolone: The Ultimate Hormone Precursor (Woodland Health). Woodland Publishing, 1997.

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Pregnenolone: A Radical New Approach to Health, Longevity, and Emotional Well-Being. Essential Science Publishing, 2000.

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Book chapters on the topic "Pregnenolone"

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Bährle-Rapp, Marina. "Pregnenolone Acetate." In Springer Lexikon Kosmetik und Körperpflege, 452. Berlin, Heidelberg: Springer Berlin Heidelberg, 2007. http://dx.doi.org/10.1007/978-3-540-71095-0_8482.

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Sih, Rakhmawati, Hosam Kamel, Mohamad Horani, and John E. Morley. "Dehydroepiandrosterone and Pregnenolone." In Hormone Replacement Therapy, 241–59. Totowa, NJ: Humana Press, 1999. http://dx.doi.org/10.1007/978-1-59259-700-0_15.

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Ritsner, Michael S., Anatoly Gibel, Yael Ratner, and Abraham Weizman. "Dehydroepiandrosterone and Pregnenolone Alterations in Schizophrenia." In Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders, 251–97. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6854-6_14.

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Baulieu, Etienne-Emile, Paul Robel, Oliver Vatier, Marc Haug, Claude Le Goascogne, and Eliane Bourreau. "Neurosteroids: Pregnenolone and Dehydroepiandrosterone in the Brain." In Receptor-Receptor Interactions, 89–104. London: Palgrave Macmillan UK, 1987. http://dx.doi.org/10.1007/978-1-349-08949-9_9.

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Baulieu, Etienne-Emile, Paul Robel, Oliver Vatier, Marc Haug, Claude Le Goascogne, and Eliane Bourreau. "Neurosteroids: Pregnenolone and Dehydroepiandrosterone in the Brain." In Receptor-Receptor Interactions, 89–104. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-5415-4_9.

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Roberts, Eugene. "Remarkable Memory-Enhancing Effects of Pregnenolone Sulfate with Pheromone-Like Sensitivity." In Neurosteroids, 337–47. Totowa, NJ: Humana Press, 1999. http://dx.doi.org/10.1007/978-1-59259-693-5_19.

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Payne, Victoria M., Jason D. Kilts, Jennifer C. Naylor, Jennifer L. Strauss, Patrick S. Calhoun, Roger D. Madison, and Christine E. Marx. "Allopregnanolone and Pregnenolone Alterations Following Pharmacological Agents in Rodents and Clinic Populations." In Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders, 369–83. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6854-6_18.

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Wakerley, J. B., and C. M. Richardson. "Differential Effects of the Neurosteroid Pregnenolone Sulphate on Oxytocin and Vasopressin Neurones in Vitro." In Advances in Experimental Medicine and Biology, 127–28. Boston, MA: Springer US, 1998. http://dx.doi.org/10.1007/978-1-4615-4871-3_13.

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Brewster, M. E., W. R. Anderson, T. Loftsson, N. Bodor, and E. Popa. "Effect of 2-Hydroxypropyl-β-Cyclodextrin Complexes of the Neurosteroids, Alfaxalone, Pregnanolone and Pregnenolone, on Various Convulsant Stimuli in the Mouse." In Proceedings of the Eighth International Symposium on Cyclodextrins, 511–14. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-011-5448-2_113.

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Roberts, Eugene, and L. Jaime Fitten. "Serum Steroid Levels in Two Old Men with Alzheimer's Disease (AD) Before, During, and After Oral Administration of Dehydroepiandrosterone (DHEA). Pregnenolone Synthesis May Become Rate-Limiting in Agin." In The Biologic Role of Dehydroepiandrosterone (DHEA), edited by M. Kalimi and W. Regelson, 43–64. Berlin, Boston: De Gruyter, 1990. http://dx.doi.org/10.1515/9783110847383-005.

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Conference papers on the topic "Pregnenolone"

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Zahari, Noor Fazila, and Ikram M. Said. "Pregnenolone from the roots of Holarrhena curtisii." In THE 2013 UKM FST POSTGRADUATE COLLOQUIUM: Proceedings of the Universiti Kebangsaan Malaysia, Faculty of Science and Technology 2013 Postgraduate Colloquium. AIP Publishing LLC, 2013. http://dx.doi.org/10.1063/1.4858747.

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