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 is close similarity in catalytic properties between human and bovine cytochromes P-450scc which suggests that the active site of the cytochrome is highly conserved.
45 citations
TL;DR: In contrast to the biphasic effect of PRL on production of androgen, PRL treatment enhanced hCG-stimulated production of progesterone in a dose-related manner without exerting an inhibitory effect.
Abstract: Prolactin (PRL) exerts both stimulatory and inhibitory effects upon testicular steroidogenesis in vivo. The direct effects of PRL on biosynthesis of testicular androgen were studied in primary cultures of testicular cells obtained from adult, hypophysectomized or neonatal, intact rats. In cells from adult animals, treatment with human chorionic gonadotropin (hCG) (10 ng/ml) significantly increased testosterone and progesterone production relative to their respective controls. In contrast, neither steroid was increased by treatment with rat PRL (rPRL) or ovine PRL (oPRL) alone. Upon addition of 0.1-3 ng/ml of either rPRL or oPRL to the hCG-treated cultures, testosterone production was progressively increased up to a maximum of 70% greater than with hCG alone. However, when PRL exceeded 3 ng/ml, the testosterone response began to decline and was 39 or 24% less than from cells treated with hCG alone at 300 ng/ml of rPRL or oPRL, respectively. A similar biphasic response pattern was observed in cells from neonatal animals. In contrast to the biphasic effect of PRL on production of androgen, PRL treatment enhanced hCG-stimulated production of progesterone in a dose-related manner without exerting an inhibitory effect. At 3 and 300 ng/ml, rPRL augmented hCG action by 2.5- and 8-fold, respectively. Similarly, in the presence of inhibitors of pregnenolone metabolism, rPRL also enhanced hCG-stimulated production of pregnenolone. Quantitation of steroid intermediates in the testosterone biosynthetic pathway revealed that the stimulatory effect of 3 ng/ml rPRL on testosterone production was associated with 1.3- and 2.8-fold increases in accumulation of androstenedione and 17 alpha-hydroxyprogesterone.(ABSTRACT TRUNCATED AT 250 WORDS)
45 citations
TL;DR: The present results agree with those of earlier studies which measured fewer steroids in follicles obtained by repeated and sequential laparotomies of sows during spontaneous cycles, but these hormone results differ from those using the PMSG/hCG-stimulated ovary, suggesting that such ovaries may not be a completely valid model for ovarian steroid hormone metabolism in the normally cycling sow.
Abstract: Ovaries were obtained from sows immediately after slaughter and were morphologically assigned to different stages of the ovarian cycle. Follicular fluid contained in the predominating follicles was analysed for ten steroid hormones by a multiple, simultaneous radioimmunoassay technique. The steroids measured were pregnenolone, progesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxyprogesterone, androstenedione, 5 alpha-dihydrotestosterone, dehydroepiandrosterone, testosterone, oestrone and oestradiol-17 beta. The concentrations of the steroids remained relatively low during the luteal stages until the mid-follicular stage when ovaries contained predominantly small to medium-sized (less than 5.0 mm in diam.) follicles. With the exception of 5 alpha-dihydrotestosterone concentrations, which remained low regardless of the size of the follicles or the stage of the cycle, the concentrations of all the steroids were significantly elevated in the transition from the mid- to late follicular stage, a period when the ovaries contained mainly large (6-10 mm diam.) follicles. Follicles at the ovulatory stage exhibited a profound decline in the concentrations of androgens and oestrogens. In contrast, the magnitude of decline in the levels of 3 progestagens, i.e. pregnenolone, progesterone and 17 alpha-hydroxyprogesterone, was much less than that for androgens and oestrogens, while the concentration of 20 alpha-dihydroprogesterone was actually elevated in the ovulatory follicles. The present results agree with those of earlier studies which measured fewer steroids in follicles obtained by repeated and sequential laparotomies of sows during spontaneous cycles. In contrast, these hormone results differ from those using the PMSG/hCG-stimulated ovary, suggesting that such ovaries may not be a completely valid model for ovarian steroid hormone metabolism in the normally cycling sow.
45 citations
TL;DR: Investigation of the uptake by 11 brain regions and appearance in blood of tritium-labeled pregnenolone and progesterone after intranasal and intravenous (IV) injection shows that therapeutic levels of neurosteroids can be delivered to the brain by intran asal administration, but that the two routes have significant differences with intranAsal administration favoring some brain regions.
45 citations
TL;DR: Comparison of P4507B1 sequences in rat, human, and two mouse species showed that one amino acid change might explain important differences in KM for 7α‐hydroxylation, and suggested that such differences might contribute to the extent of immune response.
Abstract: In human and murine lymphoid organs, circulating 3 beta-hydroxysteroids, including pregnenolone (PREG), dehydroepiandrosterone (DHEA), and epiandrosterone (EPIA), are 7 alpha-hydroxylated by a cytochrome P450 identified in the hippocampus as P4507B1. Mouse and human lymphoid organs produced different patterns of 3 beta-hydroxysteroid 7 alpha-hydroxylation with the absence of pregnenolone and epiandrosterone hydroxylation in human and mouse, respectively. Both 7 alpha-hydroxy-DHEA and 7 alpha-hydroxy-EPIA triggered a significant increase of antitetanus toxoid and anti-Bordetella pertussis toxins IgGs production in cultures of activated B + T cells derived from human tonsils, whereas both 7 alpha-hydroxy-PREG and 7 alpha-hydroxy-DHEA increased the immune response in mouse. Paracrine action of 7 alpha-hydroxysteroids resulted from their production in cells of the lymphoid organs. Comparison of P4507B1 sequences in rat, human, and two mouse species showed that one amino acid change might explain important differences in KM for 7 alpha-hydroxylation, and suggested that such differences might contribute to the extent of immune response.
45 citations