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 results suggest the sequence A leads to B leads to C leads to D as the basic mechanism for the conversion of cholesterol to pregnenolone as the initial process involving an initial oxygen attack of cholesterol at C-22.
100 citations
TL;DR: Characterization of the newly described human hydroxysteroid sulfotransferase SULT2B1 isoforms shows that these enzymes are selective for the sulfation of 3 beta-hydroxysteroids, such as pregnenolone, epiandrosterone, DHEA, and androstenediol.
100 citations
TL;DR: Activation of 7 alpha-hydroxylation by increased close contacts of astrocytes and after glucocorticoid treatment suggested that the regulated production of 7alpha-hydroxysteroids was a key event for the neuroprotection conferred by neurosteroids.
Abstract: Robert Morfin Laboratoire de Biotechnologie Conservatoire National des Arts et M~tiers 75003, Paris, France Luboslav St6rka Institute of Endocrinology 116 94 Prague 1, Czech Republic I. Neurosteroid Metabolism in the Brain II. 7~-Hydroxylation Studies in the Brain III. 7/3-Hydroxylation Studies in the Brain 1V. 7~-Hydroxy-DHEA and 7/3-Hydroxy-DHEA as Native Anti-glucocorticoids V. The Brain and Other Organs VI. Sex Steroid Metabolism in the Brain VII. Concluding Remarks References The neurosteroids pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are precursors for both oxidized and hydroxylated metabolites in the brain. Thus, brain production of 7-hydroxylated derivatives is sec- ond to that in the liver, and P4507Bl-containing hippocampus is the major site for 7c~-hydroxylation. Other P450s and/or oxido-reductive mechanisms may be responsible for 7/3-hydroxylation. In addition to regulating neuros- teroid brain levels, when produced, the 7-hydroxylated derivatives of PREG and DHEA were investigated for antiglucocorticoid-mediated neuropro- tective potencies, and both 7c~- and 7/3-hydroxy-DHEA were efficient in preventing the nuclear uptake of [3H]dexamethasone-activated glucocor- ticoid receptor in brain cells. Activation of 7c~-hydroxylation by increased close contacts of astrocytes and after glucocorticoid treatment suggested that the regulated production of 7c~-hydroxysteroids was a key event for the neuroprotection conferred by neurosteroids. ~.~2001 Academic Press.
99 citations
TL;DR: It is reported that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly.
Abstract: Embryonic cell movement is essential for morphogenesis and the establishment of body shapes, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.
99 citations
TL;DR: Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females, suggesting that the major male/female differences in brain pregnenolate and PROG levels may contribute to the sex differences observed in brain mitochondrial function.
Abstract: Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.
98 citations