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: The following acetylenic steroids appear to be the first reported mechanism-based inhibitors of cytochrome P-450scc: 20-(1,5-hexadiynyl)-5-pregnen-3 beta, 20 alpha-diol under turnover conditions completely inactivates the enzyme with a half-time of 11 min.
42 citations
TL;DR: The novel finding of theregulation of a 7 alpha-hydroxylase by IL-1 beta (and tumor necrosis factor alpha) suggests a unique role for cytokines in the regulation of cholesterol metabolism in the ovary and possibly other tissues.
42 citations
TL;DR: It is revealed that neuroactive steroids may exert multiple modulatory activities on the GABA(A) receptor borne by melanotrope cells, and the effect of steroids on the current evoked by GABA is rapid, reversible, stereospecific and not mediated through the benzodiazepine binding site of theiazepine receptor.
42 citations
TL;DR: It is made the surprising observation that this coactivator can induce the expression of CYP11A1 and CYP17A1, key rate-limiting enzymes involved in the initial steps of steroidogenesis.
Abstract: The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha is involved in the coordinate induction of changes in gene expression in the liver that enable a homeostatic response to alterations in metabolic state, environmental cues, and nutrient availability. In exploring the specific pathways under PGC-1alpha regulation in the liver, we have made the surprising observation that this coactivator can induce the expression of CYP11A1 and CYP17A1, key rate-limiting enzymes involved in the initial steps of steroidogenesis. Both of these enzymes function to produce C(19)-steroids, converting cholesterol into pregnenolone, and then to dehydroepiandrosterone (DHEA). Estrogen-related receptor (ERR)-alpha mediates PGC-1alpha's induction of CYP11A1 and binds within the first intron of the CYP11A1 gene. Both ERR-alpha and hepatocyte nuclear factor-4alpha are required for PGC-1alpha-mediated induction of CYP17A1, and specific binding sites for these receptors have been identified in the regulatory regions of this gene. The potential physiological significance of these observations was highlighted in rats where fasting induced hepatic expression of PGC-1alpha and CYP17A1 and was associated with an increase in hepatic levels of DHEA. These data suggest that DHEA could be playing a role as an intracellular signaling molecule involved in modulating hepatic activity in response to fasting conditions.
42 citations
TL;DR: Cholesterol side chain cleavage has been shown to be dependent on the electron carrier chain involving a cytochrome P-450 reductase system, flavoprotein and nonheme iron-protein of the ferredoxin type, and the oxygen-activating cyto Chrome oxidase system.
42 citations