Topic
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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TL;DR: Results indicate that insulin exerts a specific action on granulosa cells to increase the FSH stimulation of estrogen and progestin production and could not be accounted for by changes in cell viability or total cell number.
80 citations
TL;DR: It is concluded that neurosteroids regulate the morphology and/or GFAP distribution of astrocytes in hippocampal slice cultures from adult rats.
Abstract: Recent evidence indicates that astroglia may be involved in the synthesis of endogenous neurosteroids. The extension of glial fibrillary acidic protein (GFAP)-immunoreactive astroglial cell processes was assessed in hippocampal slice cultures from adult gonadectomized male rats under the influence of the neurosteroids dehydroepiandrosterone, dehydroepiandrosterone sulfate, dehydroepiandrosterone estereate, pregnenolone, pregnenolone sulfate, and pregnenolone oleate. The effects of neurosteroids were compared to those induced by the gonadal steroids testosterone, 17 beta-estradiol and progesterone. Astrocytes in hippocampal slice cultures had a morphology that was indistinguishable from that observed in the hippocampus fixed in situ. Castration of adult male rats resulted in a significant decrease in the extension of GFAP-immunoreactive processes, both in tissues fixed in situ and in slice cultures. In contrast, incubation of slice cultures from gonadectomized animals with pregnenolone, pregnenolone sulfate, 17 beta-estradiol, and testosterone enhanced the extension of GFAP-immunoreactive processes. While other steroids tested did not affect this parameter, dehydroepiandrosterone and its sulfate and estereate derivatives induced the transformation of astroglial cells into hypertrophic and highly GFAP immunoreactive cells with the morphological characteristics of reactive astroglia. We conclude that neurosteroids regulate the morphology and/or GFAP distribution of astrocytes in hippocampal slice cultures from adult rats.
79 citations
TL;DR: Induction and co-induction of drug-metabolizing enzymes are generally considered as adaptive responses leading to more efficient elimination and detoxication of xenobiotics such as benzo(a)pyrene, however, at 'non-physiological' levels of exposure enzyme induction may lead to increased toxic risk.
Abstract: 1. Isozymes of the cytochromes P-450, UDP-glucuronosyl transferases (UDPGT) and glutathione S-transferases appear to be differentially inducible by prototype inducers, such as 3-methylcholanthrene (MC), phenobarbital, pregnenolone 16 alpha-carbonitrile and clofibrate. 2. Mechanisms of induction include both transcriptional and post-transcriptional control. MC-type inducers (representing a large number of planar polycyclic aromatics, beta-naphthoflavone and polyhalogenated aromatics) bind with high affinity to the Ah receptor which controls gene expression similar to steroid hormone receptors. The Ah receptor controls the expression of several drug metabolizing enzymes. For example, both cytochrome P450 IA1 and UDPGT-1 appear to be co-induced by inducers with widely differing potencies, such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin, 1,2,3,7,8-pentachloro-dibenzo-p-dioxin and benz(a)anthracene. Much less is known about the mechanism of action of other inducer prototypes. 3. Induction and co-induction of drug-metabolizing enzymes are generally considered as adaptive responses leading to more efficient elimination and detoxication of xenobiotics such as benzo(a)pyrene. For example, when the mutagenicity of benzo(a)pyrene and benzo(a)pyrene-3,6-quinone was studied in the Ames test, glucuronidation or glutathione conjugation (concomitant with cytochrome P-450-dependent reactions) markedly decreased their mutagenicity. The protective effect was more pronounced with the homogenate S9 fraction of MC-treated rats. However, at 'non-physiological' levels of exposure enzyme induction may lead to increased toxic risk.
79 citations
TL;DR: Results indicate that A1248 down-regulates the testicular androgenesis by an acute inhibition of 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/lyase, and 17β-Hydroxysteroids dehydrogen enzyme activities.
Abstract: Polychlorinated biphenyls (PCBs) are complex mixtures of congeners that exhibit carcinogenic and toxicant activities in a variety of mammalian tissues. Here, we studied the acute in vivo and in vitro effects of a commercially used PCB product, Aroclor 1248 (A1248), a mixture of tri-, tetra-, and pentachloro congeners. Single intraperitoneal (i.p.) or bilateral intratesticular (i.t.) injections of A1248 decreased serum androgen levels in both groups 24 h after injection. Chorionic gonadotropin-stimulated androgen production by acute testicular cultures from both groups was also reduced, and progesterone production was attenuated in cultures from i.t.-treated animals. The capacity of the postmitochondrial fractions from testes of i.t.-treated animals to convert pregnenolone to progesterone and progesterone to testosterone was reduced as well. In vitro studies revealed that a 10- to 15-min exposure of postmitochondrial testicular fractions and intact interstitial cells from normal animals to A1248 in a subnanomolar concentration range was sufficient to attenuate the conversion of pregnenolone to progesterone and progesterone to testosterone. At micromolar concentrations, A1248 added in vitro also inhibited the conversion of Delta(4)-androstendione to testosterone without affecting the viability of interstitial cells. These results indicate that A1248 down-regulates the testicular androgenesis by an acute inhibition of 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/lyase, and 17beta-hydroxysteroid dehydrogenase activities.
79 citations
TL;DR: It is demonstrated that StAR is a target for serine phosphorylation mediated by protein kinase A (PKA), a process that is essential to maximizing StAR activity, and StAR functions as a cholesterol transfer protein that does not require a protein receptor or co-factor, suggesting that St AR acts directly on lipids of the outer mitochondrial membrane to promote cholesterol translocation.
79 citations