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Pregnenolone

About: Pregnenolone is a research topic. Over the lifetime, 3539 publications have been published within this topic receiving 126444 citations. The topic is also known as: (3b)-3-hydroxy-Pregn-5-en-20-one & 3-Hydroxypregn-5-en-20-one.


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Journal ArticleDOI
TL;DR: As with adrenocorticotropin pretreatment in vivo, addition of cardiolipin in vitro enhances adrenal mitochondrial pregnenolone synthesis and apparent binding of cholesterol to cytochrome P-450scc.

46 citations

Journal ArticleDOI
TL;DR: The action of Preg‐S on the activity of the mesencephalic dopaminergic projection to the nucleus accumbens is studied which is considered one of the biological substrates of motivation and reward.
Abstract: Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently of peripheral sources. Clinical studies in humans have associated some of these hormones with a generic sensation of 'well-being' and with pathologies such as depression. In rodents, the neurosteroid pregnenolone sulphate (Preg-S) has been shown to present antidepressant-like effects. These observations suggest that neurosteroids could interact with reward-related processes, mood and motivation. However, the possible neural substrates of such an effect remain unclear. In this report, we studied the action of Preg-S on the activity of the mesencephalic dopaminergic projection to the nucleus accumbens which is considered one of the biological substrates of motivation and reward. Both the direct effect of Preg-S and the influence of this hormone on the dopaminergic response to the pharmacological reward provided by the opiate morphine, were studied by means of microdialysis. Pregnenolone sulphate dose-dependently increased dopamine release in the nucleus accumbens. Furthermore, this hormone doubled the dopaminergic response to morphine. These effects were observed for Preg-S doses of 100, 200, and 400 pmol injected intracerebroventricularly. The stimulant effect of Preg-S on dopamine could mediate some of the behavioural effects of neurosteroids and in particular the interaction of these hormones with mood and motivation.

46 citations

Journal ArticleDOI
TL;DR: Findings indicate that activin A probably exerts a partial inhibitory effect on cholesterol side-chain cleavage cytochrome P450 (P450scc) activity, and potentially enhances 3 beta-HSDI activity in Leydig cells.
Abstract: In the present study, we evaluated the effect of the homodimer activin A on immature porcine Leydig cell functions in primary culture Activin A (05-100 ng/ml) reduced hCG-stimulated dehydroepiandrosterone (DHEA) accumulation in a dose- and time-dependent manner, with a maximal inhibitory effect (58% decrease) at 20 ng/ml (8 x 10(-10) M) Activin A was found not to control steroidogenesis, either through a modulation of the gonadotropin LH/hCG binding or low-density lipoprotein cholesterol binding and internalization However, activin A significantly decreased pregnenolone (p less than 0002) and DHEA (p less than 0001) formation (evaluated in the presence of 10(-5) M of WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase [3 beta-HSDI]activity) in Leydig cells maximally stimulated with hCG (3 ng/ml, 3 h) or incubated in the presence of 22R-hydroxycholesterol (5 micrograms/ml, 2 h) These findings indicate that activin A probably exerts a partial inhibitory effect on cholesterol side-chain cleavage cytochrome P450 (P450scc) activity On the other hand, activin A significantly (p less than 0001) enhanced the conversion of exogenous pregnenolone and DHEA (500 ng/ml) but not of progesterone and androstenedione (500 ng/ml) into testosterone, suggesting that activin A potentially enhances 3 beta-HSDI activity in Leydig cells Activin A action on 3 beta-HSDI activity was found to be closely related to that of transforming growth factor-beta 1 (TGF beta 1), since both activin A (20 ng/ml) and TGF beta 1 (2 ng/ml) induced a comparable and non-additive increase in 3 beta-HSDI activity(ABSTRACT TRUNCATED AT 250 WORDS)

46 citations

Journal ArticleDOI
TL;DR: It is established that from the onset of estrogen synthesis the fetal ovary possesses all of the enzymes necessary to form estrogens from pregnenolone, including sufficient 3β-hydroxysteroid dehydrogenase-Δ4,5-isomerase activity.
Abstract: Two aspects of the differentiation of the fetal rabbit gonad have been studied. First, the ability of the fetal ovary to synthesize 17β-estradiol from [7-3H]pregnenolone was measured. By day 18 of gestation, the fetal ovary was capable of synthesizing 17β-estradiol from radioactive pregnenolone (5 mol 2 h-1 mg protein-1), thus establishing that from the onset of estrogen synthesis the fetal ovary possesses all of the enzymes necessary to form estrogens from pregnenolone, including sufficient 3β-hydroxysteroid dehydrogenase-Δ4,5-isomerase activity. Second, a method was developed to estimate the rate of cholesterol side chain cleavage activity by measuring the total amount of six steroids [progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, Δ5-androstenediol (5-androstene-3β,17β-diol), and testosterone] produced in 2-h incubations of fetal rabbit gonads. Cholesterol side chain cleavage activity in fetal testes was linear with time up to 2 h and with increasing concentrations of hCG up to a ...

46 citations

Book ChapterDOI
TL;DR: The chapter presents the most advanced scheme for the enzymatic transformation of cholesterol to pregnenolone, which is by far the major precursor of all the steroid hormones in the adrenal gland, ovary, and testis.
Abstract: Publisher Summary Pregnenolone is the C21 steroid closest in structure to cholesterol, which is the most abundant sterol in the Eutheria. C21 steroid is by far the major precursor of all the steroid hormones in the adrenal gland, ovary, and testis. Cholesterol sulfate converts to various steroidal sulfates in humans in vivo and to pregnenolone sulfate by bovine adrenocortical mitochondria in vitro. The chapter presents the most advanced scheme for the enzymatic transformation of cholesterol to pregnenolone. Cholesterol derivatives with only a hydroxyl at C-20 in the side chain appear not to have been isolated from natural sources. The premise that the hydroxylated derivatives of cholesterol served as better substrates than cholesterol itself was based on the more rapid transformation of the labeled precursors, which were not always studied at specified substrate concentrations. A better understanding of the mechanism of the conversion of cholesterol to pregnenolone awaits further investigation.

46 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202344
202255
202124
202028
201950
201835