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 influence of steroidal and non-steroidal antioestrogenic compounds on the effect of systemically administered oestradiol (OE2) and diethylstilboestrol (DES) was investigated in adult male rats with intact gonads. In this animal model, oestrogens induced the NADP-dependent cytoplasmic activity and prevented the inductive action of androgens on NADP-dependent microsomal activity of renal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Simultaneous administration of tamoxifen (0.5 mg/day) with OE2 (5 microgram/day) or DES (10 microgram/day) for 10 days completely blocked the inductive effect of OE2 on cytoplasmic 3 alpha-HSDH, whereas, in the case of the microsomal enzyme, the repressive effects of OE2 and DES were antagonized only to 28 and 16% respectively. Simultaneous administration of 5 alpha-dihydrotestosterone (DHT; 0.5 mg/day) for 10 days antagonized the inductive effect of OE2 on the cytoplasmic enzyme activity to 86% and completely by-passed the repressive effects of OE2 and DES on the microsomal enzyme activity. It is concluded that oestrogenic induction of renal cytoplasmic 3 alpha-HSDH involves an oestrogen receptor mechanism which, in this animal model, can be antagonized by tamoxifen. In contrast, oestrogenic repression of renal microsomal 3 alpha-HSDH is obviously the consequence of the strong antigonadotrophic activity of oestrogens leading to subsequent repression of testicular androgen secretion by mechanisms which can be only weakly antagonized by tamoxifen. Exogenous DHT, even in the presence of OE2 or DES, completely compensates for this centrally mediated deficit of peripheral androgen.
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PMID:Action of oestrogens and antioestrogens on oestrogen-inducible cytoplasmic and androgen-inducible microsomal activity of 3 alpha-hydroxysteroid dehydrogenase in male rat kidney. 52 34

In earlier studies, two distinct molecules, 20 alpha-HSD-I and 20 alpha-HSD-II, responsible for 20 alpha-HSD activity of pig adrenal cytosol were purified to homogeneity and characterized [S. Nakajin et al., J. Steroid Biochem. 33 (1989) 1181-1189]. We report here that the purified 20 alpha-HSD-I, which mainly catalyzes the reduction of 17 alpha-hydroxyprogesterone to 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one, catalyzes 3 alpha-hydroxysteroid oxidoreductase activity for 5 alpha (or 5 beta)-androstanes (C19), 5 alpha (or 5 beta)-pregnanes (C21) in the presence of NADPH as the preferred cofactor. The purified enzyme has a preference for the 5 alpha (or 5 beta)-androstane substrates rather than 5 alpha (or 5 beta)-pregnane substrates, and the 5 beta-isomers rather than 5 alpha-isomers, respectively. Kinetic constants in the reduction for 5 alpha-androstanedione (Km; 3.3 microM, Vmax; 69.7 nmol/min/mg) and 5 beta-androstanedione (Km; 7.7 microM, Vmax; 135.7 nmol/min/mg) were demonstrated for comparison with those for 17 alpha-hydroxyprogesterone (Km; 26.2 microM, Vmax; 1.3 nmol/min/mg) which is a substrate for 20 alpha-HSD activity. Regarding oxidation, the apparent Km and Vmax values for 3 alpha-hydroxy-5 alpha-androstan-17-one were 1.7 microM and 43.2 nmol/min/mg, and 1.2 microM and 32.1 nmol/min/mg for 3 alpha-hydroxy-5 beta-androstan-17-one, respectively. 20 alpha-HSD activity in the reduction of 17 alpha-hydroxyprogesterone catalyzed by the purified enzyme was inhibited competitively by addition of 5 alpha-DHT with a Ki value of 2.0 microM. Furthermore, 17 alpha-hydroxyprogesterone inhibited competitively 3 alpha-HSD activity with a Ki value of 150 microM.
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PMID:3 alpha-hydroxysteroid dehydrogenase activity catalyzed by purified pig adrenal 20 alpha-hydroxysteroid dehydrogenase. 154 86

5 alpha-Dihydrotestosterone 3 alpha(beta)-hydroxysteroid dehydrogenase [3 alpha(beta)-HSDH] [EC 1.1.1.50/EC 1.1.1.51] which catalyses the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol was purified to an apparent homogeneous state using cytosol of three human hyperplastic prostates by a 4-step purification procedure. After each purification step 3 alpha-HSDH activity was coincident with 3 beta-HSDH activity. On average, specific 3 alpha-HSDH activity was enriched 856-fold, specific 3 beta-HSDH activity 749-fold compared to human prostatic cytosol using anion exchange, hydrophobic interaction, gel filtration and affinity chromatography. Examination of the purified enzyme by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) revealed a single protein band with silver staining. The molecular weight of the enzyme was estimated as 33 kDa by SDS-polyacrylamide gel electrophoresis and as 28 kDa by Sephacryl S-200 gel filtration indicating that the native 3 alpha(beta)-HSDH is a monomer. In the presence of the preferred co-factor, NADPH, the purified enzyme had a mean apparent Km for 5 alpha-DHT of 3.9 microM and a Vmax of 93.3 nmol (mg protein)-1 h-1 with regard to 3 alpha-HSDH activity, and a Km of 6.3 microM and a Vmax of 20.6 nmol (mg protein)-1 h-1 with regard to 3 beta-HSDH activity.
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PMID:Purification and properties of the 5 alpha-dihydrotestosterone 3 alpha(beta)-hydroxysteroid dehydrogenase from human prostatic cytosol. 160 44

Leydig cell progenitors contain significant concentrations of androgen receptors. When the metabolism of DHT to 3 alpha-DIOL is blocked, DHT stimulates testosterone production by Leydig cell progenitors, most probably via an androgen receptor dependent mechanism. Rapid metabolism by 3 alpha-HSD may limit the potency of exogenous DHT to stimulate differentiation of Leydig cell progenitors in vitro. Insulin-like growth factor-I enhances androgen production by purified immature Leydig cells. The elevated sensitivity of immature Leydig cells versus adult Leydig cells to IGF-I stimulation indicates that this peptide hormone has a role in their differentiation during puberty.
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PMID:Hormonal control of Leydig cell differentiation. 178 69

A 3 alpha-reducing activity of 5 alpha-dihydrotestosterone (5 alpha-DHT) was found in pig adrenal cytosol. The enzyme (3 alpha-hydroxysteroid dehydrogenase: 3 alpha-HSD) has been purified to homogeneity from pig adrenal cytosol by ammonium sulfate precipitation followed by DEAE-cellulose, 2', 5'-adenosine diphosphate-Sepharose and Sephadex G-100 column chromatographies. The molecular weight was estimated to be 33,000 and 39,000 by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric point was estimated to be 8.5 by isoelectric focusing. The Km and Vmax values for 5 alpha-DHT in the reduction were 10.2 microM and 10.6 nmol/min/mg. The enzyme utilized reduced nicotinamide adenine dinucleotide phosphate (NADPH) or reduced nicotine amide adenine dinucleotide (NADH) in the reduction as a cofactor, but it preferentially required NADPH rather than NADH. Furthermore, the purified enzyme catalyzed not only 3 alpha-reduction of 5 alpha-DHT (9.65 nmol/min/mg), but also catalyzed 20 alpha-reduction of 17 alpha-hydroxyprogesterone (0.58 nmol/min/mg). The enzyme activity of 3 alpha-HSD was strongly inhibited by Hg2+, but it was not inhibited by medroxyprogesterone acetate and some anti-inflammatory agents. No remarkable differences was demonstrated between 3 alpha-HSD and 20 alpha-HSD activity under the influence of heat treatment, divalent cation, anti-inflammatory agents and some inhibitory steroids. These results strongly suggest that 3 alpha-HSD purified from pig adrenal cytosol is a bi-functional enzyme catalyzing 3 alpha- and 20 alpha-HSD activities.
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PMID:[Purification and some properties of 3 alpha-hydroxysteroid dehydrogenase from pig adrenal cytosol]. 180 59

Pig testicular 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) has also 3 alpha- and 3 beta-HSD (3 alpha/beta-HSD) activities. The purified 20 beta-HSD preparation from neonatal pig testes could catalyze the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) in the presence of beta-NADPH to 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol at the ratio of 4:3, and the specific 3 alpha/beta-HSD activity of 20 beta-HSD for 5 alpha-DHT was about 10 or 15 times larger than the 20 beta-HSD activities for 17 alpha-hydroxypregn-4-ene-3,20-dione (17 alpha-hydroxyprogesterone) or progesterone, respectively. The result indicates that the testicular 20 beta-HSD has high 3 alpha(axial, 3R)- and 3 beta(equatorial, 3S)-HSD activity. The testicular 20 beta-HSD could catalyze the reversible conversion of various 5 alpha- or 5 beta-dihydrosteroids which have a 3-carbonyl or 3-hydroxyl group with beta-NADP(H) as the preferred cofactor. The enzyme transferred the 4-proS hydrogen of NADPH to the 5 alpha-DHT for both 3 alpha- and 3 beta-hydroxylation and it was the same as the 20 beta-hydroxylation of 17 alpha-hydroxyprogesterone. Although the 3 alpha/beta-HSD activity has been known to be present in 3 alpha,20 beta-HSD of Streptomyces hydrogenans, the enzymological properties for 3 alpha/beta-HSD activity catalyzed by testicular 20 beta-HSD were different from the properties for 3 alpha/beta-HSD activity catalyzed by prokaryotic 3 alpha, 20 beta-HSD with respect to the specificity of the catalytic reaction and the cofactor requirement.
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PMID:20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: 3 alpha/beta-hydroxysteroid dehydrogenase activities catalyzed by highly purified enzyme. 206 95

To evaluate the action of 5 alpha-androstane-3 alpha,17 beta-diol(3 alpha-diol) in rat submandibular gland, 5 alpha-reductase, 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) and oxidative 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDO) activities, and trypsin-like protease activities, were assayed in control, castrated and 3 alpha-diol injected rats. 3 alpha-Diol (1 mg/kg) was injected subcutaneously in castrated male rats daily for 7 days. A 47% decrease of 5 alpha-reductase activity in the nuclei and a 30% decrease of 3 alpha-HSD(O) activities in the cytosol were shown after castration. 3 alpha-Diol restored the 5 alpha-reductase and 3 alpha-HSD(O) activities to 82 and 140% of the control submandibular gland, respectively. 3 alpha-Diol raised the trypsin-like protease activity to near control values in the submandibular gland of castrated rats. Morphological observations also revealed a distinct effect of 3 alpha-diol on the number of granules of granular duct cells. It is concluded that 3 alpha-diol has an androgenic action in the rat submandibular gland. It stimulates the 3 alpha-HSD(O). The 3 alpha-HSD(O) in its turn may be responsible for DHT accumulation in the cells.
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PMID:Androgenic actions of 5 alpha-androstane-3 alpha,17 beta-diol in rat submandibular gland. 235 33

In order to study the mechanism of action of androgen on pubic and scalp hair, we established these and skin epithelial cells in culture. Because 5 alpha-reductase has been suspected of playing a role in hair growth, we tested the possibility that these cells differ in their pattern of androgen metabolism. Furthermore, we tested the hypothesis that androgen exerts its distinctive effects on these hairs by differentially regulating keratin or DNA synthesis. Anagen hairs of men and women were plucked from the pubis or scalp vertex and were studied using an epithelial cell culture technique. DHT formation from [3H]T cultured skin cells increased in the following order: epidermal less than scalp less than pubic less than fibroblasts = 0.8:2.8:8.1:71%/mg DNA/min, respectively. Androstanediols were minor [3H]DHT metabolites of all these skin cell types. The only feature that distinguished among the cultured epithelial cells was the ratio of apparent 5 alpha-reductase (5 alpha-R) to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity: this was significantly greater (P less than 0.05) in cultured pubic hair cells than in scalp hair or epidermal cells. Cultured scalp and pubic hair cells resembled freshly plucked hair follicle cells in their keratin pattern. 46, 50, 56 and 58 kdalton bands constituted 99% of the total keratins. This keratin pattern and the polygonal cell shape were also similar to that of cultured epidermal cells. However, this keratin pattern was distinctly different from that of hair shafts which have 53 and 63 kdalton keratins. Dihydrotestosterone did not affect the keratin pattern, pattern of incorporation of [35S]cysteine or [35S]methionine, or rates of protein synthesis or cell proliferation in cultured hair cells. Although the higher apparent 5 alpha-R/17 beta-HSD ratio of cultured pubic than of scalp hairs is compatible with modulation of hair development by androgen, these studies militate against the possibility that androgens directly affect hair cell proliferation or protein synthesis in pubic or scalp hair.
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PMID:Studies of androgen metabolism and action in cultured hair and skin cells. 242 54

The well-known hormone dependency of the normal human prostate and of BPH and prostatic carcinoma stimulated the study of cellular events which would possibly lead to specific steroid hormone patterns under the respective prevailing condition. In extending earlier observations on a significant DHT and E2 accumulation especially in stromal nuclei of BPH recent data on the uptake and metabolism of adrenal androgens clearly underline the important differential role of either stromal or epithelial cells. Epithelium and stroma of BPH contained a quantitatively different pattern of steroid metabolizing enzymes. This dualism of enzyme activity favours the conversion of testosterone to DHT in the stroma while androgens of adrenal origin are metabolized mainly in BPH epithelium. Further to quantitative data on the intracellular distribution of the three sex steroid classes (estrogens, androgens, adrenal androgens) and to Km and Vmax values of the respective steroid metabolizing enzymes in question (5 alpha-reductase, 3 alpha/beta-HSDH, 17 beta-HSDH, sulfatase, aromatase) the impact of antihormones (cyproterone acetate) on the intratissular distribution and on the in vivo cytosolic and nuclear binding of DHT as well as on its biological implications will be discussed. The data present a complicated picture, which points to special roles of epithelial and stromal cells and allow speculations on the relative importance of testicular and adrenal androgens and estrogens for the development and maintenance of both normal and diseased human prostates. Furthermore, the determination of intratissular steroid concentrations can be an important tool to understand and to ground a rational basis for a hormonal treatment of prostatic tumors.
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PMID:Intratissular androgens in benign prostatic hyperplasia and prostatic cancer. 243 5

The effects of various quantities of Ba, Be, Ca, Cd, Co, Cu, Mg, Mn, Sr, Zn and EDTA on the formation of 5 alpha-reduced metabolites of testosterone (T) substrate and of 3 alpha-/3 beta-reduced metabolites of 5 alpha-dihydrotestosterone substrates by homogenates of 6 human hyperplastic prostate glands were studied in incubations at pH 7.4 with NADPH-generating system. Effects of these cations and EDTA on the VM and KM of the 5 alpha-reductase and 3 alpha-/3 beta-hydroxysteroid dehydrogenases (-HSD) were also measured. Quantities of 5 alpha-reduced T metabolites were significantly increased by Cd, Cu and Zn supplementations. These increments were shown to result from significant augmentations of the VM but no change in KM of the NADPH-dependent 5 alpha-reductase. Quantities of 3 alpha-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations and resulted from an increase of the KM of the NADPH-dependent 3 alpha-HSD by Cd and both an increase of KM and a decrease of VM by Cu. Quantities of 3 beta-reduced DHT metabolites were significantly decreased by Cd and Cu supplementations. Increase of the KM of the NADPH-dependent 3 beta-HSD by Cd was found significant while Cu both increased the KM and decreased the VM of the enzyme. EDTA-related changes in 5 alpha-reductase activity were shown to result from the EDTA-induced decrease of the pH of the medium. No effect of EDTA was observed on the activities of both 3 alpha/3 beta-HSD.
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PMID:Testosterone metabolism by homogenates of human prostates with benign hyperplasia: effects of zinc, cadmium and other bivalent cations. 620 Jul 4


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