Relevant bibliographies by topics / Pregnenolone

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Academic literature on the topic 'Pregnenolone'

Author: Grafiati
Published: 4 June 2021
Last updated: 15 June 2025

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Journal articles on the topic "Pregnenolone"

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Gao, Huaze, Zachary Magin, Nia Fogelman, Rajita Sinha, Gustavo A. Angarita, and Verica Milivojevic. "Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings." Life 14, no. 11 (2024): 1483. http://dx.doi.org/10.3390/life14111483.

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Substance use disorders (SUDs), including cocaine use disorder (CUD), have significant negative health risks and impose a substantial social burden, yet effective treatments are limited. Pregnenolone, a neuroactive steroid precursor, has been shown to reduce alcohol craving and normalize stress biology in individuals with CUD, but its clinical utility has been questioned due to limited data on bioavailability and the stability of blood levels in humans. Thus, this pilot study aimed to determine whether twice-daily oral pregnenolone (PREG) at 300 mg/day and 500 mg/day versus placebo in week two of PREG administration led to stable increased plasma pregnenolone levels in individuals with CUD. Seven treatment-seeking individuals with CUD, enrolled in an eight-week double-blind clinical trial, were randomized to receive placebo (n = 2) or pregnenolone at 300 mg/day (n = 3) or 500 mg/day (n = 2). For the first two weeks of the eight-week trial, participants were admitted to an inpatient Clinical Neuroscience Research Unit for repeated serial sampling of plasma pregnenolone concentrations over a 32.5 h period in week two of their inpatient stay while taking their assigned study drug under observation. Pregnenolone levels showed a significant main effect of the medication group (p = 0.039), with sustained higher levels in the 300 mg (p = 0.018) and 500 mg (p = 0.035) groups compared to placebo, and no significant difference between the two pregnenolone dosing groups. Moreover, correlation analyses showed that after observed study medication dosing on repeated sampling day 1, levels of pregnenolone were highly associated across time, with strong, positive correlations between time of dosing and 2 h (r = 0.80, p = 0.031), 4 h (r = 0.80, p = 0.031), 6 h (r = 0.86, p = 0.013), and 8 h post-dosing (r = 0.97, p < 0.001). These findings from this pilot study suggest that chronic twice-daily/“bis in die” (b.i.d.) oral administration of pregnenolone at both 300 mg/day and 500 mg/day achieved stable and reliable elevated plasma pregnenolone levels over 32.5 h in individuals with CUD, thereby supporting the good bioavailability of pregnenolone in these samples. These data indicate that twice-daily chronic dosing may overcome any potential concerns of poor bioavailability and rapid metabolism of pregnenolone in humans, and support further clinical investigations into pregnenolone’s role in the treatment of cocaine use disorders.
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McKay, S. A., G. Jenkin та 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, № 2 (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 (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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Morsy, Mohamed A., Seham A. Abdel-Gaber, Sahar A. Mokhemer, et al. "Pregnenolone Inhibits Doxorubicin-Induced Cardiac Oxidative Stress, Inflammation, and Apoptosis—Role of Matrix Metalloproteinase 2 and NADPH Oxidase 1." Pharmaceuticals 16, no. 5 (2023): 665. http://dx.doi.org/10.3390/ph16050665.

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The clinical usefulness of doxorubicin (DOX) is limited by its serious adverse effects, such as cardiotoxicity. Pregnenolone demonstrated both anti-inflammatory and antioxidant activity in animal models. The current study aimed to investigate the cardioprotective potential of pregnenolone against DOX-induced cardiotoxicity. After acclimatization, male Wistar rats were randomly grouped into four groups: control (vehicle-treated), pregnenolone (35 mg/kg/d, p.o.), DOX (15 mg/kg, i.p, once), and pregnenolone + DOX. All treatments continued for seven consecutive days except DOX, which was administered once on day 5. The heart and serum samples were harvested one day after the last treatment for further assays. Pregnenolone ameliorated the DOX-induced increase in markers of cardiotoxicity, namely, histopathological changes and elevated serum levels of creatine kinase-MB and lactate dehydrogenase. Moreover, pregnenolone prevented DOX-induced oxidative changes (significantly lowered cardiac malondialdehyde, total nitrite/nitrate, and NADPH oxidase 1, and elevated reduced glutathione), tissue remodeling (significantly decreased matrix metalloproteinase 2), inflammation (significantly decreased tumor necrosis factor-α and interleukin 6), and proapoptotic changes (significantly lowered cleaved caspase-3). In conclusion, these findings show the cardioprotective effects of pregnenolone in DOX-treated rats. The cardioprotection achieved by pregnenolone treatment can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic actions.
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Jiang, Jingjing, Xue Liu, Xiaotian Liu, 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 (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, et al. "Equine fetal adrenal, gonadal and placental steroidogenesis." Reproduction 154, no. 4 (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, et al. "The Spontaneous Ala147Thr Amino Acid Substitution within the Translocator Protein Influences Pregnenolone Production in Lymphomonocytes of Healthy Individuals." Endocrinology 150, no. 12 (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, et al. "Pregnenolone Can Protect the Brain from Cannabis Intoxication." Science 343, no. 6166 (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 (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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Bracci, Massimo, Laura Zingaretti, Margherita Martelli, et al. "Alterations in Pregnenolone and Testosterone Levels in Male Shift Workers." International Journal of Environmental Research and Public Health 20, no. 4 (2023): 3195. http://dx.doi.org/10.3390/ijerph20043195.

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Steroid hormone levels are closely related to the endogenous circadian rhythm induced by sleep–wake and dark–light cycles. Shift work that disrupts the circadian rhythm may influence the levels of steroid hormones. The association between shift work and alterations in female sex steroid hormone levels has been studied, but little is known about testosterone and its precursor pregnenolone levels in male shift workers. The present study investigated serum pregnenolone and testosterone levels in a group of shift and daytime male workers. All participants were sampled at the beginning of the morning shift. Lower levels of serum pregnenolone and total testosterone were found in the shift workers compared to the daytime workers. Variations in pregnenolone levels may have consequences for well-being, and they might produce consequences for the levels of hormones downstream of the steroid hormone cascade, such as testosterone. The low levels of testosterone found in shift workers demonstrate the perturbative effect of shift work on testosterone serum levels, which may be independent and/or related to pregnenolone synthesis.
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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<br>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<br>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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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.<br>Donald Doyle, Committee Member ; Harish Radhakrishna, Committee Member ; Alfred Merrill, Committee Member ; Marion Sewer, Committee Chair Includes bibliographical references.
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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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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"

1

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

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Pregnenolone: Nature's feel good hormone. Avery Pub. Group, 1997.

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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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Mahler, Philip. Longitudinalverlauf von Pregeneolon und 17-OH Pregnenolon bei Früh- und Neugeborenen in der Neonatalperiode. 2004.

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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. 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. Humana Press, 1999. http://dx.doi.org/10.1007/978-1-59259-700-0_15.

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Tariq, Syed H., Hosam Kamel, and John E. Morley. "Dehydroepiandrosterone and Pregnenolone." In Endocrine Replacement Therapy in Clinical Practice. Humana Press, 2003. https://doi.org/10.1007/978-1-59259-375-0_18.

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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. 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. 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. 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. 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, et al. "Allopregnanolone and Pregnenolone Alterations Following Pharmacological Agents in Rodents and Clinic Populations." In Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders. 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. 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. Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-011-5448-2_113.

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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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Eldeeb, Khalil, Allyn C. Howlett, Victor M. Pulgar, et al. "Diphenylpyraline derivative JKH10 behaves as a CB1 receptor agonist and docks at cholesterol and pregnenolone binding sites." In ASPET 2024 Annual Meeting Abstract. American Society for Pharmacology and Experimental Therapeutics, 2024. http://dx.doi.org/10.1124/jpet.568.130969.

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Bilan, Dmitri, Sergiu Cojocari, Natalia Sucman, Eughenia Stingaci, and Fliur Macaev. "Transforming the five-membered ring d in a pregnenolone derivative into a six-membered ring through skeletal rearrangement." In Scientific seminar with international participation "New frontiers in natural product chemistry". Institute of Chemistry, Republic of Moldova, 2023. http://dx.doi.org/10.19261/nfnpc.2023.ab22.

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In pursuit of obtaining steroid derivatives containing a triazole moiety in their structure, a series of reactions was conducted (Figure 1). In these reactions, an intermediate compound was the corresponding azide 3, which was subsequently involved in a reaction with the required alkyne to form a 1,2,3-triazole. In click chemistry reactions, it is well-known that catalysts are one-valent copper salts, which can be generated in situ from copper(II) salts. However, the NMR spectra of the main product, isolated from the reaction mass, did not match the expected results.Figure 1. The procedure for synthesizing azides 3 and 4 Upon analyzing the collected data from 1H, 13C, 15N, HSQC, HMBC, and DEPT spectra, it was concluded that under these conditions, a skeletal rearrangement occurs, where the fivemembered ring D expands to a six-membered one, forming a new compound. To confirm this hypothesis, the starting compound 3 was mixed under similar conditions without the addition of a reagent. As a result, the same compound was isolated, and its spectral data corresponded to the structure of 5, which was confirmed through X-ray structural analysis too.Figure 2. The mechanism of the skeletal rearrangement The mechanism of the skeletal rearrangement of steroid derivatives in the presence of copper(I) ions is presented in Figure 2.
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Reports on the topic "Pregnenolone"

1

Meidan, Rina, and Robert Milvae. Regulation of Bovine Corpus Luteum Function. United States Department of Agriculture, 1995. http://dx.doi.org/10.32747/1995.7604935.bard.

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The main goal of this research plan was to elucidate regulatory mechanisms controlling the development, function of the bovine corpus luteum (CL). The CL contains two different sterodigenic cell types and therefore it was necessary to obtain pure cell population. A system was developed in which granulosa and theca interna cells, isolated from a preovulatory follicle, acquired characteristics typical of large (LL) and small (SL) luteal cells, respectively, as judged by several biochemical and morphological criteria. Experiments were conducted to determine the effects of granulosa cells removal on subsequent CL function, the results obtained support the concept that granulosa cells make a substaintial contribution to the output of progesterone by the cyclic CL but may have a limited role in determining the functional lifespan of the CL. This experimental model was also used to better understand the contribution of follicular granulosa cells to subsequent luteal SCC mRNA expression. The mitochondrial cytochrome side-chain cleavage enzyme (SCC), which converts cholesterol to pregnenolone, is the first and rate-limiting enzyme of the steroidogenic pathway. Experiments were conducted to characterize the gene expression of P450scc in bovine CL. Levels of P450scc mRNA were higher during mid-luteal phase than in either the early or late luteal phases. PGF 2a injection decreased luteal P450scc mRNA in a time-dependent manner; levels were significantly reduced by 2h after treatment. CLs obtained from heifers on day 8 of the estrous cycle which had granulosa cells removed had a 45% reduction in the levels of mRNA for SCC enzymes as well as a 78% reduction in the numbers of LL cells. To characterize SCC expression in each steroidogenic cell type we utilized pure cell populations. Upon luteinization, LL expressed 2-3 fold higher amounts of both SCC enzymes mRNAs than SL. Moreover, eight days after stimulant removal, LL retained their P4 production capacity, expressed P450scc mRNA and contained this protein. In our attempts to establish the in vitro luteinization model, we had to select the prevulatory and pre-gonadotropin surge follicles. The ratio of estradiol:P4 which is often used was unreliable since P4 levels are high in atretic follicles and also in preovulatory post-gonadotropin follicles. We have therefore examined whether oxytocin (OT) levels in follicular fluids could enhance our ability to correctly and easily define follicular status. Based on E2 and OT concentrations in follicular fluids we could more accurately identify follicles that are preovulatory and post gonadotropin surge. Next we studied OT biosynthesis in granulosa cells, cells which were incubated with forskolin contained stores of the precursor indicating that forskolin (which mimics gonadotropin action) is an effective stimulator of OT biosynthesis and release. While studying in vitro luteinization, we noticed that IGF-I induced effects were not identical to those induced by insulin despite the fact that megadoses of insulin were used. This was the first indication that the cells may secrete IGF binding protein(s) which regonize IGFs and not insulin. In a detailed study involving several techniques, we characterized the species of IGF binding proteins secreted by luteal cells. The effects of exogenous polyunsaturated fatty acids and arachidonic acid on the production of P4 and prostanoids by dispersed bovine luteal cells was examined. The addition of eicosapentaenoic acid and arachidonic acid resulted in a dose-dependent reduction in basal and LH-stimulated biosynthesis of P4 and PGI2 and an increase in production of PGF 2a and 5-HETE production. Indomethacin, an inhibitor of arachidonic acid metabolism via the production of 5-HETE was unaffected. Results of these experiments suggest that the inhibitory effect of arachidonic acid on the biosynthesis of luteal P4 is due to either a direct action of arachidonic acid, or its conversion to 5-HETE via the lipoxgenase pathway of metabolism. The detailed and important information gained by the two labs elucidated the mode of action of factors crucially important to the function of the bovine CL. The data indicate that follicular granulosa cells make a major contribution to numbers of large luteal cells, OT and basal P4 production, as well as the content of cytochrome P450 scc. Granulosa-derived large luteal cells have distinct features: when luteinized, the cell no longer possesses LH receptors, its cAMP response is diminished yet P4 synthesis is sustained. This may imply that maintenance of P4 (even in the absence of a Luteotropic signal) during critical periods such as pregnancy recognition, is dependent on the proper luteinization and function of the large luteal cell.
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