Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of cultured midpregnancy mouse ovarian cells to synthesize progesterone de novo and from oxogenous pregnenolone has been assessed. The conversion of pregnenolone to progesterone is almost completely blocked by cyanoketone, a known inhibitor of delta5,3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity, but is unaffected by aminoglutethimide, which inhibits the cholesterol side-chain cleavage enzyme complex (desmolase). Since there is little metabolism of the formed progesterone, the ability of ovarian cells to convert exogenous pregnenolone to progesterone in vitro reflects the activity of 3beta-HSD in these cells. Cultured ovarian cells are also capable of endogenous progesterone production in the absence of added pregnenolone, although the absolute amount of progesterone produced is considerably less than that produced from exogenous pregnenolone. Since endogenous progesterone accumulation is almost completely blocked by the addition of aminoglutethimide to the culture medium, it is concluded that this response does represent de novo progesterone synthesis. Neither bovine luteinizing hormone (LH) nor human chorionic gonadotrophin (hCG) affects 3beta-HSD activity in cultured ovarian cells. The ability of the cells to secrete or to further metabolize the progesterone formed is also unaffected. However, both LH and hCG stimulate endogenous progesterone production within one hour of their addition to the culture medium. The stimulation, 2-10 fold in several experiments, can be maintained for at least six days of culture, and is not a result of an increase in the growth rate of the ovarian cells. As would be expected, the stimulation is blocked by the addition of aminoglutethimide to the culture medium. Taken together, these facts suggest that gonadotrophic hormones stimulate progesterone production by ovarian cells specifically by their action at steps prior to the conversion of pregnenolone to progesterone.
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PMID:Gonadotrophin stimulation of progesterone synthesis by midpregnancy mouse ovarian cells in vitro. 95 70

The hamster, a rodent possessing adrenal 17 alpha-hydroxylase activity, was used to study the effect of ACTH on the regulation of cortisol formation in vivo. The characterization of the mRNA and protein of hamster adrenal steroidogenic enzymes revealed close similarities between this animal and other mammalian species. The hamster adrenal RNA hybridized in a single band to cDNA probes for bovine adrenal P450scc, P450(17 alpha), P450c21, to mouse adrenal P450(11 beta), and to pig testis 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in the areas of 2.2, 2.0, 2.3, 2.0, and 2.1 kilobases, respectively. Immunoblotting analyses revealed the presence of single protein bands reacting with antibodies to bovine P450scc, P450c21, porcine P450(17 alpha), or human placental 3 beta HSD in the areas of 52, 55, 51, and 41 kilodaltons, respectively, whereas two protein bands were detected at 48 and 52 kilodaltons with the antibody to bovine P450(11 beta). After stimulation with ACTH injected at 5-h intervals over 20 h, plasma cortisol levels, which were already increased 2.5 h after the first injection, remained elevated for the duration of treatment and returned to control values 15 h after the last injection. The ratios of plasma cortisol to corticosterone were 1.5, 3.9, and 7 at 0, 2.5, and 5 h after the first injection and continued to rise to a value of 11 at 15 h after multiple injections. This ratio returned to control values 15 h after cessation of either the short term (one injection) or long term (five injections) treatment, indicating a control mechanism favoring cortisol formation upon ACTH stimulation. Of the adrenal enzyme systems examined, only three were directly affected by ACTH treatment. The mRNA level of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase, the key precholesterol regulatory step, increased after ACTH administration within 2.5 h and remained elevated during the entire study period. ACTH provoked a rapid and sustained increase in P450scc mRNA levels, which decreased very slowly after cessation of treatment without reaching control values 30 h after the last injection. Meanwhile, ACTH treatment caused no changes in the amount of adrenal cytochrome P450scc protein during treatment and 30 h after its cessation. Therefore, we postulate that factors other than newly synthesized P450scc protein participate in the control of this rate-limiting step. The high P450scc mRNA levels observed suggest stabilization of mRNA and posttranscriptional events affecting its catabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo effects of adrenocorticotropin on hamster adrenal steroidogenic enzymes. 132 21

The expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P45017 alpha), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was studied in bovine placenta and fetal adrenal glands throughout gestation. The levels of expression of these enzymes were much lower in the placenta than in the adrenals by Western and Northern analyses. The levels of P450scc, however, remained relatively constant in bovine placenta and fetal adrenal glands at all gestational stages studied. In contrast, P45017 alpha expression was higher in both the placenta and the fetal adrenal glands during the early stages of pregnancy, but declined markedly in both tissues through the period of midgestation. The expression of P45017 alpha increased markedly in the fetal adrenal glands in late gestation. The levels of 3 beta HSD were extremely low in placental tissues, but were higher in the fetal adrenals, where they were found to be slightly elevated in early and late gestation compared to those in midgestational stages. Immunocytochemical examination of the levels of P45017 alpha and 3 beta HSD in the fetal adrenal glands correlated with the results of Western and Northern analyses. In addition, the morphology and distribution of these two enzymes in the developing bovine fetal adrenal glands indicated that while the early activated gland is functional relative to the ability to secrete steroids, structural and functional organization more typical of mature adrenal glands is not achieved until the time of activation of the fetal adrenals in late gestation.
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PMID:Expression of steroidogenic enzymes in the bovine placenta and fetal adrenal glands throughout gestation. 137 10

The aim of this investigation was to isolate, characterize, and culture the small and large luteal cell subpopulations forming the corpus luteum of the pregnant rat. Since the large luteal cells are extremely fragile and do not survive standard cell dispersion, a method which allows the survival and the long-term culture in serum-free media of small and large cells was developed. The two luteal cell populations differed not only by their size but also by their morphology in culture. The small luteal cells (12-20 mu in diameter) are characterized by a large oval nucleus, contain few lipid droplets and have a stellate shape. In contrast, the large luteal cells have a smaller spherical nucleus, high lipid content, and do not flatten out completely in culture, most probably due to the abundance of lipid droplets. Both luteal cell types express 3 beta HSD and the cytochrome P450 enzymes involved in steroidogenesis. However, it is the lipid filled large luteal cells that secrete the most progesterone, androgen, and estradiol; express greater amounts of P450scc and P450AROM; and possess more PRL and LH receptors. Despite the greater expression of LH receptor in the large luteal cells, small and large luteal cells responded to LH with equal increase in steroidogenic output. In serum free culture, luteal cells produced progesterone for up to 20 days; however, an exogenous source of cholesterol was a prerequisite for maximal progesterone secretion. The pattern of progesterone secretion by cultures of small and large luteal cells differed remarkably from that of mixed cell population. When nonsteroidogenic corpus luteum cells were cocultured with the large luteal cells, a severalfold increase in progesterone secretion was observed. This stimulation occurred even when cells were cocultured in the absence of exogenous source of cholesterol. In summary, a successful method was developed to disperse, isolate, and independently culture the two luteal cell populations forming the rat corpus lutem. The results indicate that the marked difference in the steroidogenic capacity of these two cell populations is due, in large part, to the difference in their size rather than to their origin in the follicle. In addition, the results have revealed an important effect of the nonsteroidogenic cells forming the corpus luteum on luteal cell steroidogenesis.
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PMID:Isolation, characterization, and culture of cell subpopulations forming the pregnant rat corpus luteum. 173 37

The regulation of mRNA levels for delta 5-3 beta-hydroxysteroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD), 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 (P450(17 alpha] and cholesterol side-chain cleavage cytochrome P450 (P450scc) was studied in primary cultures of mouse Leydig cells. Treatment of Leydig cells with 8-bromo-cAMP (cAMP) was essential for expression of P450(17 alpha) mRNA, but not for 3 beta HSD. Treatment with cAMP caused a decrease in basal levels of 3 beta HSD mRNA. The addition of aminoglutethimide (AG), an inhibitor of cholesterol metabolism, to the cAMP-treated cultures resulted in increased expression of both 3 beta HSD and P450(17 alpha) mRNA levels. The addition of testosterone or the androgen agonist mibolerone to cAMP- plus AG-treated cultures reduced 3 beta HSD and P450(17 alpha) mRNA to levels comparable to those observed when cells were treated with cAMP only. The glucocorticoid dexamethasone reduced both basal and cAMP- plus AG-induced increases in 3 beta HSD mRNA, but not in P450(17 alpha) mRNA. Estradiol at a concentration of 1 microM had no effect on cAMP- plus AG-induced 3 beta HSD or P450(17 alpha) mRNA levels. The role of protein synthesis in mediating the cAMP induction of 3 beta HSD, P450(17 alpha), and P450scc was investigated. The addition of cycloheximide (10 micrograms/ml) to cAMP-treated cultures for 24 h completely suppressed both constitutive and cAMP-induced 3 beta HSD mRNA levels. Cycloheximide also repressed cAMP-induced levels of P450(17 alpha) to 12% of levels observed in the absence of cycloheximide. In sharp contrast, 24-h treatment with cycloheximide did not suppress cAMP induction of P450scc mRNA, but reduced basal levels by approximately 50%. A time course of induction by cAMP (50 microM) of P450(17 alpha) and P450scc mRNA showed very similar rates of increase in P450(17 alpha) and P450scc mRNA, with the greatest increase occurring between 12 and 24 h of treatment. The results of the study demonstrate that in normal mouse Leydig cells steady state levels of mRNA for 3 beta HSD, P450(17 alpha), and P450scc are differentially regulated. cAMP is required for maximal levels of all three mRNAs. There is high constitutive expression of 3 beta HSD and P450scc mRNA, while expression of P450(17 alpha) mRNA is absolutely dependent on cAMP stimulation. Endogenously produced testosterone negatively regulates the expression of cAMP-induced P450(17 alpha) and 3 beta HSD, while the glucocorticoid dexamethasone negatively regulates 3 beta HSD and P450scc.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple mechanisms for regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5----delta 4-isomerase, 17 alpha-hydroxylase/C17-20 lyase cytochrome P450, and cholesterol side-chain cleavage cytochrome P450 messenger ribonucleic acid levels in primary cultures of mouse Leydig cells. 187 81

A genetic difference in maximal testosterone production in Leydig cells relates to differences in the genotype at the P450scc locus. The genetic relationship between the P450scc gene, the amount of Leydig cell P450scc protein, and maximal testosterone production was determined in the F2 generation of mice derived from SWR/J mice (SWR), a high Leydig cell testosterone-producing strain, and from C3H/HeJ (C3H), a low Leydig cell testosterone-producing strain. A restriction fragment length polymorphism was identified in the P450scc gene between SWR and C3H mice. This restriction fragment length polymorphism was used to identify F2 mice homozygous for the SWR or the C3H alleles of the P450scc gene. The two types of homozygous mice were compared with regard to maximal testosterone production and the amounts of P450scc, P45017 alpha, and 3 beta-hydroxysteroid dehydrogenase isomerase (3 beta HSD) proteins. Maximal testosterone production, amounts of P450scc and 3 beta HSD were significantly greater in the SWR than in the C3H progenitor mice. In the F2 mice, homozygous for either the SWR or the C3H allele of P450scc, the differences in maximal testosterone production and the amount of P450scc protein were comparable to the differences in the two progenitor strains. A significant correlation (r = 0.75; P less than 0.01) was found between the amount of P450scc protein and maximal testosterone production. No differences in the amounts of P45017 alpha or 3 beta HSD were observed in the F2 males.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genotype at the P450scc locus determines differences in the amount of P450scc protein and maximal testosterone production in mouse Leydig cells. 198 Sep 36

The levels of expression of mRNA species encoding cholesterol side-chain cleavage cytochrome P-450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha], aromatase cytochrome P-450 (P-450AROM), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) were examined in human follicles and corpora lutea (CL) throughout the menstrual cycle. Tissues were obtained from women undergoing hysterectomy and oophorectomy. The largest follicle or the CL was dissected from the ovary depending on whether the surgery was performed in the follicular or luteal phase. The day of the cycle was determined by onset of last menstrual period and was confirmed by endometrial histology. Total RNA was examined by Northern blot analysis, using as probes specific 32P-labeled cDNA inserts encoding each human enzyme. Early follicles demonstrated detectable mRNA for both P450scc and P450(17 alpha), but not for P450AROM or 3 beta HSD. P450AROM was detectable late in the follicular phase and appeared markedly induced in the CL. 3 beta HSD was detectable only in the CL. Levels of P450(17 alpha) mRNA remained relatively unchanged throughout the cycle, whereas P450scc mRNA levels were greatly increased in the CL. The presence of P450(17 alpha) mRNA in the human CL is of interest, since it is absent from the bovine CL, and this is consistent with the ability of the human, but not the bovine, CL to synthesize 17 alpha-hydroxyprogesterone and estrogens. The fact that P450AROM expression is highest in CL is surprising, since plasma estrogen levels are highest during the late follicular phase of the cycle, and may suggest that CL estrogen biosynthesis is limited by 17 alpha-hydroxylase or 17,20-lyase activities.
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PMID:Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. 218 Sep 73

Incomplete masculinization due to a deficiency of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was investigated in siblings aged 4 years (Case 1) and 12 years (Case 2). Diagnosis was based on increased ratios of androstenedione (A) to testosterone (T) in blood, and impaired reduction of A to T by 17 beta-HSD in vitro in the testes. Impairment was total in Case 2 but partial in Case 1. Case 2 also showed deficient conversion of dehydroepiandrosterone (DHA) to androstenediol and of oestrone to oestradiol by 17 beta-HSD which were normal in Case 1. Oxidation of T to A by 17 beta-HSD and conversion of 17 alpha-hydroxyprogesterone to A by 17,20 desmolase were normal in the testes of both siblings. 3 beta-HSD conversion of DHA to A was normal in Case 1, but markedly increased in Case 2. In contrast to testicular findings, 17 beta-HSD reduction of A to T in genital skin fibroblasts from Case 2 was normal and diagnosis would not have been possible from studies of measurements of this enzyme in skin. The severity of the testicular 17 beta-HSD deficiency in the peripubertal compared with the prepubertal sibling suggests either considerable intra-familial variation in the extent of the enzyme defect or that puberty may aggravate this disorder. The normal reductive action of 17 beta-HSD in skin, despite impaired action in testes, suggests involvement of more than one iso-enzyme.
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PMID:Incomplete masculinization due to a deficiency of 17 beta-hydroxysteroid dehydrogenase: comparison of prepubertal and peripubertal siblings. 282 Jun 22

For purposes of establishing suitable controls in studies of patients with a suspected enzyme deficiency, activities of enzymes involved in the biosynthesis of testosterone were compared in testes of patients with androgen insensitivity syndrome (AIS) and normally differentiated males with carcinoma of the prostate (Ca prostate) or testis (Ca testis). Activities of 17,20-desmolase and of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were higher in the testes of pre-, peri- or postpubertal patients with AIS than in elderly men (58-80 yr) with Ca prostate. Activities of 17 beta-HSD (reductive direction) and 3 beta-HSD tended to be higher in peri- or postpubertal than in prepubertal patients with AIS. Activity of 3 beta-HSD was low in the patient with Ca testis. In a peripubertal (12 yr) patient with incomplete masculinization due to a severe deficiency of 17 beta-HSD, reductive activity of 17 beta-HSD was very low compared with that of patients with Ca prostate, Ca testis or AIS. In contrast, in testes from the younger sibling (4 yr), in whom the deficiency of 17 beta-HSD was less severe, 17 beta-HSD reduction of dehydroepiandrosterone was as high as that of men with Ca prostate, yet deficient in comparison with that of more closely age-matched patients with AIS. This emphasizes the desirability of using age-matched tissue for control purposes in enzyme studies.
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PMID:Steroid metabolism in testes of patients with incomplete masculinization due to androgen insensitivity or 17 beta-hydroxysteroid dehydrogenase deficiency and normally differentiated males. 289 56

Gonadal homogenates of rainbow trout from D(ay) 60, D100 and D200 after fertilization have been incubated in vitro in the presence of dehydroepiandrosterone-3H to demonstrate 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and delta 5,4-isomerase activity, of pregnenolone-3H to assess the synthesis of "progestins" and of androstenedione-3H to determine oestrogen synthesis in the ovaries and the formation of androgens in the testes. Histologically indifferent gonads from D50 contained 3 beta-HSD, delta 5,4-isomerase and 17 alpha-hydroxylase, indicating a capacity to synthesize progestins. Ovaries from D100 possessed the same enzymes as D50 gonads; those from D200 had, in addition, 17 beta-HSD and aromatase, indicative of oestrogen synthesis. Unlike the D50 gonads, the D100 testes also contained 17 alpha, 20-desmolase and 11 beta-hydroxylase, showing a capacity to synthesize androgens. 17 beta-HSD was only demonstrated in D200 testes. The possible role of androgens and progestins in the regulation of gonadal sex differentiation in rainbow trout has been discussed. Ultrastructural and enzymecytochemical investigations have demonstrated stroma (Leydig) cells as sources of steroidogenesis in rainbow trout testis from D100 onwards. The appearance of big mitochondria with many tubular cristae in those cells synchronized with the appearance of 11 beta-hydroxylase activity. Obvious steroidogenic sites could not be demonstrated in younger gonads and developing ovaries.
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PMID:Steroidogenesis in the gonads of rainbow trout fry (Salmo gairdneri) before and after the onset of gonadal sex differentiation. 621 51


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