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: There was a definite trend for the free dehydroepiandrosterone values to be higher in women, and the possible significance of these observations is discussed.
179 citations
TL;DR: Synthesis of P450PCN is a specific glucocorticoid-responsive liver function evoked by a novel mechanism readily distinguishable from the classic glucoc Corticoid receptor pathway.
179 citations
TL;DR: The present data indicate the existence of two mRNAs encoding rat 3 beta-HSD and their differential tissular distribution in both steroidogenic and peripheral tissues.
178 citations
TL;DR: Evidence is presented that astrocytes and neurons in the cerebral cortex of neonatal rat brain express P450c17 and synthesize DHEA from pregnenolone, suggesting that as in gonads and adrenal, D HEA is biosynthesized in the brain by a P 450c17-dependent mechanism.
Abstract: Dehydroepiandrosterone (DHEA) is abundantly found in brain tissues of several species, including human. However, the cellular origin and pathway by which DHEA is synthesized in brain are not yet known. We have, therefore, initiated pilot experiments to explore gene expression of cytochrome P450 17α-hydroxylase (P450c17), the key steroidogenic enzyme for androgen synthesis, and evaluate DHEA production by highly purified astrocytes, oligodendrocytes, and neurons. Using RT-PCR, we have demonstrated for the first time that astrocytes and neurons in the cerebral cortex of neonatal rat brain express P450c17. The presence of P450c17 in astrocytes and neurons was supported by the ability of these cells to metabolize pregnenolone to DHEA in a dose-dependent manner as determined by RIA. These data were further confirmed by production of androstenedione by astrocytes using progesterone as a substrate. However, cortical neurons express a low transcript of P450c17 messenger RNA and produce low levels of DHEA and andr...
178 citations
TL;DR: The monooxygenase activities, the sensitivity to in vitro alpha-naphthoflavone and metyrapone, the results of steroid metabolism, and slab gel electrophoresis are strong indications for multiplicity of human liver cytochrome P-450.
Abstract: Microsomes were prepared from human livers obtained from renal donors of various ages and both sexes. Their drug-metabolizing capacity was measured and compared to that of rat liver microsomes. The following parameters were investigated: cytochrome P-450, cytochrome B5, NADPH-cytochrome c reductase, epoxide hydrolase, aryl hydrocarbon hydroxylase, benzphetamine N-demethylase, p-nitroanisole-O-demethylase, ethoxycoumarin-O-deethylase, steroid-16 alpha-hydroxylase. In addition, the metabolism of benzo(a)pyrene, progesterone, pregnenolone, testosterone, dehydroepiandrosterone and estradiol was studied in detail in vitro. The inhibitory effect of metyrapone and alpha-naphthoflavone on 7-ethoxycoumarin-O-deethylase was measured. The microsomal proteins of both species were separated by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate. The following conclusions were drawn from the results obtained. Human liver microsomes can be stored under optimal conditions for the measurement of a large variety of enzymic activities. Human liver microsomes are able to metabolize the various xenobiotics used as substrates with a rate similar to that of female rat liver microsomes. No sex-linked difference in enzymic activity was observed in human microsomes. Significant differences in benzo(a)pyrene and steroid metabolism were registered when human and rat liver microsomes were compared. The monooxygenase activities, the sensitivity to in vitro alpha-naphthoflavone and metyrapone, the results of steroid metabolism, and slab gel electrophoresis are strong indications for multiplicity of human liver cytochrome P-450.
176 citations