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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: The results provide the first evidence for the regulation of neurosteroid biosynthesis by key proteins involved in the etiology of AD and suggest that pathogenic factors may induce neurodegeneration in humans through the reduction of the synthesis of endogenous neuroprotective neurosteroids in nerve cells.
Abstract: Studies performed with animals suggest neurosteroid involvement in neuroprotection. However in humans, the role of neurosteroidogenesis in the regulation of degenerative processes is unknown. To determine whether cellular factors intervening in degenerative mechanisms may interfere with the process of neurosteroidogenesis in humans, we combined pulse-chase experiments with HPLC and continuous flow scintillation detection to compare neurosteroid production in normal and transfected SH-SY5Y cells with key proteins involved in Alzheimer's disease (AD). Microscope analyses revealed that cell morphology was unchanged in stably transfected SH-SY5Y cells overexpressing human native tau (hTau40), mutant tau (P301L), and wild-type amyloid precursor protein (APPwt) compared to controls. Biochemical investigations showed that hTau40 enhanced progesterone (PROG), 17OHPROG, testosterone, and 3alpha-androstanediol neosynthesis from pregnenolone. In contrast, tau with the pathogenic P301L mutation was devoid of action on neurosteroidogenesis. Overexpression of APPwt inhibited PROG formation, did not affect 17OHPROG and testosterone, but increased 3alpha-androstanediol and estradiol synthesis. Extracellular treatment of control cells with aggregated amyloid peptide mimicked the action of APPwt expression on PROG but not on 3alpha-androstanediol and estradiol production. Moreover, PROG biosynthesis in APPwt cells was up-regulated in the presence of a gamma-secretase inhibitor. Our results provide the first evidence for the regulation of neurosteroid biosynthesis by key proteins involved in the etiology of AD. The data suggest that pathogenic factors may induce neurodegeneration in humans through the reduction of the synthesis of endogenous neuroprotective neurosteroids in nerve cells.

43 citations

Journal ArticleDOI
TL;DR: Xenopus CYP17 rapidly converted pregnenolone and progesterone to dehydroepiandrosterone (DHEA) and androstenedione, respectively, and introduces the unusual paradigm whereby germ cells may be responsible for producing important steroids used to mediate their own maturation.

43 citations

Journal ArticleDOI
TL;DR: The purpose of this review will be to summarize briefly some background material on StAR and then attempt to update several recent and interesting findings on the StAR protein.
Abstract: In response to trophic hormone stimulation of steroidogenic adrenal and gonadal cells, the acute biosynthesis of steroid hormones occurs in the order of minutes to tens of minutes and can be contrasted to chronic regulation, which occurs on the order of hours. The steroidogenic acute regulatory (StAR) protein is an indispensable component in the acute regulatory phase and functions by rapidly mediating the transfer of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where it is cleaved to pregnenolone, the first steroid formed. This transfer of cholesterol constitutes the rate-limiting step in steroidogenesis. To underscore its importance, mutations in the StAR gene have been shown to be the only cause of the potentially fatal disease lipoid congenital adrenal hyperplasia, in which affected individuals synthesize virtually no steroids. Since the cloning of the murine cDNA in 1994, many observations have substantiated the critical role of StAR in regulated steroidogenesis. The purpose of this review will be to summarize briefly some background material on StAR and then attempt to update several recent and interesting findings on the StAR protein.

43 citations

Journal ArticleDOI
TL;DR: In 33 pregnancies, blood samples were collected from the maternal vein and umbilical cord artery and vein during cesarean section performed at 37–41 weeks of gestation, demonstrating marked utilization of steroid sulfates by the placenta from the fetal circulation at term.
Abstract: In 33 pregnancies, blood samples were collected from the maternal vein and umbilical cord artery and vein during cesarean section performed at 37–41 weeks of gestation. Serum concentrations of unconjugated steroids and PRL were measuredby RIA, and concentrations of steroid sulfates were measured by gas chromatography. Nineteen women (group A) were operated on in the absence of signs of the beginning of labor. Paired comparisons revealed large cord arteriovenous differences in the serum levels of steroid sulfates (nanograms per ml, mean ± SEM): pregnenolone sulfate, 98 ± 25; dehydroepiandrosterone sulfate, 160 ± 51; 16a-hydroxydehydroepiandrosterone sulfate, 621 ± 150; and estriol sulfate, 169 ± 20, demonstrating marked utilization of steroid sulfates by the placenta from the fetal circulation at term. Smaller but significant cord arteriovenous differences were also found in the serum levels of unconjugated pregnenolone (3.0 ± 1.1), dehydroepiandrosterone (2.15 ± 0.53), and cortisol (10.0 ± 2.4). On the co...

42 citations

Journal ArticleDOI
TL;DR: Pregnenolone and progesterone were estimated in extracts from adrenal glands of rats by gas— liquid chromatography by gas-liquid chromatography with error bars of 0.1.
Abstract: 1. Pregnenolone and progesterone were estimated in extracts from adrenal glands of rats by gas—liquid chromatography. 2. In unstressed rats their concentrations were found to be smaller than that of corticosterone. 3. Acute stress caused an increase in the concentrations of these steroids which paralleled that of corticosterone.

42 citations


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