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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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Journal ArticleDOI
TL;DR: Kinetic analyses of 17-hydroxylase and 17,20-desmolase activities have been performed on human adrenal microsomes, compatible with the suggestion that increased enzyme synthesis mediated by ACTH and differential inhibition by endogenous steroids may, in part, account for developmental changes in adrenal hormone secretion.
Abstract: Kinetic analyses of 17-hydroxylase and 17,20-desmolase activities have been performed on human adrenal microsomes from 12 individuals, aged 1-60 yr. The median Michaelis constant of 17-hydroxylase for the substrate pregnenolone was 0.09 microM, and that of 17,20-desmolase for the substrate 17-hydroxypregnenolone was 0.12 microM. The median maximum velocity of 17-hydroxylase (0.25 nmol/mg X min) was significantly greater than that of the desmolase (0.13 nmol/mg X min). There was no significant correlation between the age of the adrenal donor and the Michaelis constant, but the maximum velocity for both activities in the single infant donor was lower than the values in older individuals. The inhibitory effects of various steroids on both enzyme activities also were studied. All steroids examined, except cortisol, competitively inhibited both enzymes. In each case the inhibition constant was higher for 17-hydroxylase than for 17,20-desmolase, indicating that C21 side-chain cleavage would be more sensitive to inhibition by endogenous steroids. The results, taken together with those of similar studies of 3 beta-hydroxysteroid dehydrogenase kinetics, are compatible with the suggestion that increased enzyme synthesis mediated by ACTH and differential inhibition by endogenous steroids may, in part, account for developmental changes in adrenal hormone secretion.

61 citations

Journal ArticleDOI
01 Oct 1996-Steroids
TL;DR: Study of the 7 alpha-hydroxylating enzyme in these tissues indicated that microsomes contained most of the activity, except for brain, where it was primarily mitochondrial, which will prove to be useful in studies of the enzyme responsible and of the mechanisms that control its activity.

61 citations

Journal ArticleDOI
TL;DR: Studies to determine estrogen-sensitive transcriptional and translational events associated with steroidogenesis in the rabbit luteal cell model offer a novel perspective for an improved understanding of the regulatory processes governing steroidogenesis.
Abstract: Substantial evidence accumulated over six decades has established that estradiol exerts a dominant stimulatory influence on the production of progesterone by luteal tissue in pseudopregnant or pregnant rabbits, beginning approximately five days after ovulation. The direct steroidogenic action of estradiol on the luteal cell is mediated by the estrogen-receptor protein complex at the nuclear level. Major effects of estradiol lie distal to cholesterol ester and the formation of lipid droplets, and proximal to cholesterol availability for translocation into cytochrome P-450 cholesterol side-chain cleavage enzyme (P-450scc). Structure-function studies corroborate this as an estrogen-sensitive segment of the steroidogenic pathway in the rabbit corpus luteum. Estradiol increases the amount of precursor available for pregnenolone production in rabbit luteal mitochondria. Whether this is because of enhanced precursor storage in the mitochondria or because of effects on intramitochondrial movement of precursor, or both, is unclear. There is a void in knowledge between events at the nuclear level in response to the estrogen stimulus and known post-translational effects at the level of cellular and subcellular organelles. Studies to determine estrogen-sensitive transcriptional and translational events associated with steroidogenesis in the rabbit luteal cell model offer a novel perspective for an improved understanding of the regulatory processes governing steroidogenesis.

61 citations

Journal ArticleDOI
TL;DR: Two subclones of MA-10 cells are used to further demonstrate the correlation between the quantity and appearance of mitochondrial proteins and the production of steroids in response to hormone treatment and show them strong candidates for the putative proteins involved in acute regulation of steroidogenesis.
Abstract: The true rate-limiting step in steroidogenesis is the delivery of cholesterol to the inner mitochondrial membrane where it is converted to pregnenolone by the cholesterol side-chain cleavage complex. This process is known to require de novo protein synthesis. We have previously described the synthesis of a family of 37, 32, and 30 kilodalton mitochondrial proteins in response to hormone stimulation in MA-10 mouse Leydig tumor cells and have proposed that these proteins are involved in the acute regulation of steroidogenesis. In this study we have used two subclones of MA-10 cells to further demonstrate the correlation between the quantity of these proteins and the production of steroids in response to hormone treatment. One of these, designated MA-10(K3), has been transfected with a mutant gene of the type 1 regulatory subunit of the cAMP-dependent protein kinase under the control of a metallothionein promoter, whereas the other, designated MA-10(P+29), is a constitutive overproducer of a cAMP-phosphodies...

61 citations

Journal ArticleDOI
TL;DR: It is concluded that androgen synthesis occurs only within somatic cells of common carp testes, and gonadotropin, and perhaps PRL, stimulates the production of steroid precursors that, under normal physiological conditions, are metabolized to androgens.
Abstract: There is a rapid shift in the steroidogenic pathway from androgen to progestogen production in spawning male common carp, Cyprinus carpio. Experiments were conducted to determine the mechanism regulating this shift using in vitro cultures of testicular fragments and isolated sperm of spermiating male carp. The levels of 11-ketotestosterone (11-KT) continually increased for 48 h with or without gonadotropin (GtH) stimulation, suggesting that 11-KT is the principal androgen produced by carp testes. Ovine prolactin (oPRL) enhanced GtH-stimulated 11-KT production, but by itself had no effect. Gonadotropin, carp pituitary extract, and pregnenolone all enhanced the production of 11-KT, testosterone (T), and 17 alpha-hydroxyprogesterone (17-P) in a dose-dependent manner. No 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) was detected in response to any of these agents; 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P) was not measured. Both 17,20 beta-P and 17,20 alpha-P inhibited 11-KT production in a dose-dependent manner in the presence of either GtH, 17-P, or T. Isolated sperm and testicular fragment preparations both produced 17,20 beta-P and approximately tenfold more 17,20 alpha-P when incubated with 17-P. Only testicular fragments, however, produced 11-KT. We conclude that androgen synthesis occurs only within somatic cells of common carp testes. GtH, and perhaps PRL, stimulates the production of steroid precursors that, under normal physiological conditions, are metabolized to androgens.(ABSTRACT TRUNCATED AT 250 WORDS)

61 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202344
202255
202124
202028
201950
201835