Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Progestins have recently been shown to augment gonadotropin-stimulated progesterone and 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) biosynthesis in cultured rat granulosa cells. The mechanism by which progestins autoregulate ovarian progestin biosynthesis was investigated by studying the modulation of pregnenolone biosynthesis as well as the activities of the enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD). Granulosa cells obtained from immature hypophysectomized, estrogen-treated rats were cultured with FSH and/or progestins. Pregnenolone production was measured in the presence of cyanoketone (10(-6) M) to inhibit 3 beta-HSD activity. Enzymatic activities of 3 beta-HSD and 20 alpha-HSD were determined in cell homogenates by direct enzyme assays. FSH stimulated pregnenolone production, while treatment with progesterone or R5020 alone was ineffective. Concomitant treatment with the progestins further enhanced FSH-stimulated pregnenolone production in a dose-dependent manner with minimal effective doses of 10(-8) and 10(-7) M for R5020 and progesterone, respectively. In FSH-primed cells, LH increased pregnenolone accumulation, and concomitant treatment with R5020 also enhanced the LH action. Furthermore, the gonadotropins stimulated the activity of 3 beta-HSD, and this effect was further enhanced by concomitant treatment with either R5020 or progesterone in a dose-dependent manner. In addition, the 20 alpha-HSD activities were enhanced by progestins in cells treated with FSH but not with LH. Thus, both natural and synthetic progestins stimulate the gonadotropin-induced progesterone production in cultured granulosa cells via enhancing the 3 beta-HSD enzyme as well as pregnenolone biosynthesis.
Steroids 1985 Dec
PMID:Progestin regulation of progesterone biosynthetic enzymes in cultured rat granulosa cells. 393 85

Dispersed adrenal cells from a 16 1/2 week anencephalic fetus, 7 fetuses with intact pituitaries and 3 adult subjects undergoing renal transplants were maintained in tissue culture and the steroidogenic responses to ACTH (0-10(3) pg/ml), with or without added estradiol (0-10(4) ng/ml) were evaluated. In the anencephalic preparation the response to ACTH was delayed, but by the fifth day production of cortisol, dehydroepiandrosterone (DHA) and DHA-sulfate was similar to that in the other cultured fetal adrenal cells. The addition of estradiol caused dose-related inhibition of cortisol production and concomitant increase in DHA and DHA-sulfate production. The adult adrenal cells in the presence of ACTH showed a much higher cortisol/DHA secretion ratio, but the addition of estradiol markedly reduced this ratio as in fetal cells. The data support the suggestion that the major factors which interact to impose the characteristic fetal pattern of adrenal steroidogenesis are ACTH and the synergistic effects of placental and intra-adrenal steroids (such as estradiol) which act to inhibit 3 beta-hydroxysteroid dehydrogenase activity.
Steroids 1983 Dec
PMID:Effects of ACTH and estradiol on steroid production by cultured adrenal cells from an anencephalic fetus and from normal adults. 609 78

Using microsomes isolated from term human placentae kinetic analyses of each of the enzymes involved in estrogen synthesis from dehydroepiandrosterone sulfate have been carried out and the following parameters were found: sulfatase, Michaelis-Menten constant (Km) = 16,000 +/- 5,000 nM, maximum velocity (Vm) = 2.0 +/- 0.5 nmol X min-1 X mg protein-1; 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), Km = 15 +/- 3 nM, Vm = 1.8 +/- 0.4 nmol X min-1 X mg protein-1; aromatase, Km = 14 +/- 4 nM, Vm = 0.12 +/- 0.02 nmol X min-1 X mg protein-1. From these values one can predict that, theoretically, the rate-limiting enzyme in estrogen synthesis from dehydroepiandrosterone sulfate (DS) should change from the sulfatase at low concentrations of substrate to the aromatase at higher concentrations. In order to test this hypothesis we developed a system which allowed the formation of estrogens from DS, dehydroepiandrosterone, and androstenedione to be measured and the appropriate intermediates to be isolated. The sulfatase was found to be rate limiting at concentrations of DS below 2 microM and the aromatase was found to be rate limiting at higher concentrations. These data may explain why previous perfusion studies of human placentae indicated the sulfatase was the rate-limiting enzyme in estrogen synthesis yet in vitro studies found that it was the aromatase. Steroids previously shown to inhibit the 3 beta-HSD were examined for their ability to inhibit the formation of estrogens from DS. Although 3 beta-HSD activity was markedly inhibited this had little effect on the overall conversion of DS to estrogens, until high concentrations of inhibitors were used. The data also underline the importance of studying enzyme systems rather than single enzymes when studying steroid synthesis.
 ...
PMID:Kinetic studies on the formation of estrogens from dehydroepiandrosterone sulfate by human placental microsomes. 623 32

Transformation of a steroidogenic mouse adrenal cell line (Y-1) by simian adenovirus SA7 produced a cell line with low apparent steroidogenic activity. The effect of ACTH and cholera toxin on cyclic AMP production was similar in both not transformed and virus-transformed cells and activity of cyclic AMP-dependent protein kinase was also similar in both cells. In transformed cells, cholesterol was metabolized to delta 5-3 beta-hydroxysteroids, mainly 20 alpha-dihydropregnenolone while in not transformed cells, the major metabolites were delta 4-3 ketosteroids (20 alpha-dihydro- and 11 beta-hydroxy-20 alpha-dihydroprogesterone). In both cell lines ACTH increased the metabolism of cholesterol. Further studies with labelled pregnenolone and progesterone revealed a loss of delta 5-3 beta-hydroxysteroid dehydrogenase/isomerase and 11 beta-hydroxylase activity in the transformed cells.
Steroids 1981 Mar
PMID:Modification of steroidogenesis in a mouse adrenal cell line (Y-1) transformed by simian adenovirus SA-7. 626 49

Decreased sperm counts and impaired sperm motility are present in a substantial proportion of men with varicocele. Elevations in the temperature of the affected testis, and increased spermatic vein estradiol (E2) concentrations have been found in some of these patients. To investigate the possibility that increases in temperature lead to a pattern of testicular steroidogenesis that results in increased E2 synthesis, we have examined the effects of temperature changes on the activities of four important testicular steroidogenic enzymes. 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase activities were measured in the microsomal fraction of rat, pig and horse testes. Incubations were performed at 34 degrees C, 36 degrees C, and 38 degrees C. The activities of all 4 enzymes increased with each 2 degrees C temperature elevation in roughly proportional amounts. We conclude that minor elevations in incubation temperature are associated with increases in the in vitro activity of four key testicular steroidogenic enzymes.
Steroids 1984 Mar
PMID:The effects of temperature on the activity of testicular steroidogenic enzymes. 633 11

Hyperprolactinemia has been associated with several reproductive disorders. To investigate whether hyperprolactinemia directly affects rat ovarian function, we examined the ovarian histopathology and the activities of the four ovarian enzymes 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase in hyperprolactinemic rats and controls. Hypophysectomized, gonadotropin-treated Fisher rats were made hyperprolactinemic by isografting pituitary glands under the kidney capsule. The control animals received skeletal muscle. The ovaries were resected, pooled according to prolactin levels and microsomal enzyme activities were measured from each pool. Prolactin (PRL) levels were 344 +/- 23 ng/ml in the hyperprolactinemic rats and 18 +/- 5 ng/ml in the controls (p less than 0.001). Estradiol concentrations were 609 +/- 47 pg/ml in the hyperprolactinemic animals and 56 +/- 13 pg/ml in the controls (p less than 0.001). Ovarian and uterine weights were significantly higher in the hyperprolactinemic rats (p less than 0.02). Ovarian histopathology demonstrated benign polycystic transformation in the hyperprolactinemic animals. Hyperprolactinemia had no effect on 3 beta-HSD, but was associated with significant decreases in the 17-OH, 17,20-D and aromatase activities when compared to controls (p less than 0.001). We conclude that prolactin has a direct effect on rat ovarian function which appears to be independent of changes in gonadotropin secretion.
Steroids 1984 Jun
PMID:The effects of prolactin on rat ovarian function. 633 28

Acute ethanol exposure has been demonstrated to inhibit testosterone synthesis both in vivo and in vitro; however, the precise step(s) affected is controversial. Using intact collagenase-dispersed interstitial cells or 10,000 xg supernatants of interstitial cell homogenates, studies were undertaken to determine whether ethanol specifically inhibited delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity. In both cellular preparations, varying concentrations of ethanol (2.2 - 652 mM) inhibited this enzyme activity. Because alcohol dehydrogenase activity was identified specifically in Leydig cells and because the inhibition of delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity by concentrations of ethanol normally observed in circulation of alcoholic men (2.2 - 65 mM) could be reversed by saturating concentrations of NAD+ (0.2 mM) or by 4-methylpyrazole (2 mM), these results suggest that the mechanism of this inhibition is by limitation of available cofactor.
Steroids 1983 Oct
PMID:Ethanol directly inhibits delta 5-3 beta-hydroxysteroid dehydrogenase-isomerase activity in rat testis interstitial cells. 638 53

The luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH (LHRHa) inhibits rat testicular testosterone secretion. To determine whether LHRHa decreases serum testosterone concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly testicular testosterone biosynthesis, we examined the effects of LHRHa on the activities of 5 key testicular steroidogenic enzymes. Thirty hypophysectomized, hOG treated rats were given either LHRHa (1 micrograms sc/day) or saline during 7 days. The LHRHa treated animals exhibited a significant decrease of serum testosterone when compared to the control group (498 +/- 37 ng/dl vs 2044 +/- 105 ng/dl, mean +/- SEM, P less than 0.001). 17-Hydroxyprogesterone serum levels were also decreased in the LHRHa treated rats (61 +/- 6 ng/dl vs 93 +/- 7 ng/dl, P less than 0.005), while serum progesterone levels were similar in both groups of animals. These changes in steroid concentrations were associated with decreases in the microsomal enzyme activities of 17-hydroxylase (37 +/- 9 vs 654 +/- 41 pmol/mg protein/min, P less than 0.001), 17,20-desmolase (103 +/- 9 vs 522 +/- 47 pmol/mg protein/min, P less than 0.001), 3 beta-hydroxysteroid dehydrogenase (1.7 +/- 0.02 vs 4.1 +/- 0.1 nmol/mg protein/min, P less than 0.001), aromatase (95 +/- 7 vs 228 +/- 6 pmol/mg protein/min, P less than 0.001) and 17-ketosteroid reductase (167 +/- 9 vs 290 +/- 18 pmol/mg protein/min, P less than 0.01) in the LHRHa treated animals. These findings indicate that LHRHa can inhibit directly rat testicular testosterone biosynthesis.
Steroids 1984 Feb
PMID:Direct effect of the luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH on rat testicular steroidogenesis. 639 51

Recent kinetic studies on the placental microsomal 3 beta-hydroxysteroid dehydrogenase have shown that apparent Km values for 3 beta-hydroxy-5-androsten-17-one (dehydroepiandrosterone) and 3 beta-hydroxy-5-pregnen-20-one (pregnenolone) are 15nM and 40nM respectively, which are orders of magnitude lower than found in earlier studies. The purpose of this study was to investigate the substrate and nucleotide specificity of the 3 beta-hydroxysteroid dehydrogenase, and the ability of various steroids to inhibit the reaction at these lower steroid concentrations. Each steroid inhibited the metabolism of the other competitively, and the Ki values obtained were not significantly different from their respective Km values. The ability of various steroids to inhibit the reaction at concentrations of 100nM was usually less than that found at micromolar concentrations. However, certain steroids showed marked inhibition. For example, estrone and estradiol-17 beta inhibit the oxidation of both substrates competitively with Ki values of between 15 and 24nM. The Km values of dehydroepiandrosterone and pregnenolone with NADP+ as cofactor are higher than those with NAD+ as cofactor and the V values are much lower. These data indicate that in human placental microsomes a single 3 beta-hydroxysteroid dehydrogenase, essentially NAD+ specific, metabolizes dehydroepiandrosterone and pregnenolone.
Steroids 1981 Jan
PMID:Substrate and nucleotide specificity of placental microsomal 3 beta-hydroxysteroid dehydrogenase. 645 19

Adrenal gland homogenates from four different strains of mice were incubated with (4-14 C)-pregnenolone and a NADPH generating system. The most important androgen synthesized was dehydroepiandrosterone; testosterone and progesterone were synthesized to a lesser extent and the production of androstenedione was very low. The highest synthetic activities were found in the high mammary tumor strain of mice (C3H x RIII) Fl; they were increased by ovariectomy, particularly when performed at two months of age. In the other strains, they were lower, specially in the low mammary tumor strain C 57 BL. However, the 3 beta-hydroxysteroid dehydrogenase / delta 5, 4 isomerase activity was not modified by ovariectomy in the high mammary tumor strain whereas it was increased in the low mammary tumor strains. These results indicate that the androgen synthesis in mouse adrenal depends on factors such as age, sex, endocrine status (ovariectomy) but also on susceptibility to mammary tumor development.
Steroids 1982 Feb
PMID:In vitro pregnenolone metabolism by mouse adrenal gland: II-Biosynthesis of androgens. 646 48


<< Previous 1 2 3 4 5 Next >>