Topic
Hydroxysteroid dehydrogenase
About: Hydroxysteroid dehydrogenase is a research topic. Over the lifetime, 1087 publications have been published within this topic receiving 28468 citations. The topic is also known as: hydroxysteroid dehydrogenase.
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TL;DR: The Y' bile acid binders are 3 alpha-HSD, which preferentially and stereospecifically catalyze the reduction of 3-oxo-bile acids to 3alpha-hydroxy bile acids.
Abstract: Rat Y' bile acid binders (33 kD) have been previously recognized as cytosolic bile acid binding proteins (Sugiyama, Y., T. Yamada, and N. Kaplowitz, 1983, J. Biol. Chem., 258:3602-3607). We have now determined that these Y' binders are 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSD), bile acid-metabolizing enzymes. 3 alpha-HSD activity copurified with lithocholic acid-binding activity after sequential gel filtration, chromatofocusing, and affinity chromatography. Three peaks of 3 alpha-HSD activity (I, II, III) were observed in chromatofocusing and all were identified on Western blot by a specific Y' binder antiserum. 3 alpha-HSD-I, the predominant form, was purified and functioned best as a reductase at pH 7.0 with a marked preference for NADPH. Michaelis constant values for mono- and dihydroxy bile acids were 1-2 microM, and cholic acid competitively inhibited the reduction of 3-oxo-cholic acid. Under normal redox conditions, partially purified 3 alpha-HSD-I and freshly isolated hepatocytes catalyzed the rapid reduction of 3-oxo-cholic to cholic acid without formation of isocholic acid, whereas the reverse reaction was negligible. The Y' bile acid binders are therefore 3 alpha-HSD, which preferentially and stereospecifically catalyze the reduction of 3-oxo-bile acids to 3 alpha-hydroxy bile acids.
62 citations
TL;DR: The results lead to the conclusion that 17beta-HSD7 is not only involved in estradiol production but plays another (and possibly more important) role as a 3-ketosteroid reductase in cholesterogenesis.
61 citations
TL;DR: Type 1 17β-HSD increases 17 β-estradiol exposure in grade 1 EC, thus supporting tumor growth, and this enzyme represents a potential therapeutic target.
Abstract: Context: The local interconversions between estrone (low activity) and 17β-estradiol (potent compound) by 17β-hydroxysteroid dehydrogenases (17β-HSDs) can lead to high 17β-estradiol generation in endometrial cancer (EC). Objective: Examine the balance between the 17β-HSDs reducing estrone to 17β-estradiol (types 1, 5, 12, and 7) and those oxidizing 17β-estradiol to estrone (2, 4, and 8), in EC. Patients and Methods: Reducing and oxidizing 17β-HSD activities (HPLC) and mRNA level (RT-PCR) were assessed in normal post-menopausal (n = 16), peritumoral endometrium (normal tissue beside cancer, n = 13), and 58 EC (29 grade 1, 18 grade 2, 11 grade 3). Results: Grade 1 EC displayed a shifted estrone reduction/17β-estradiol oxidation balance in favor of 17β-estradiol compared with controls. This was more pronounced among estrogen receptor-α (ER-α)-positive biopsies. Type 1 17β-HSD mRNA (HSD17B1 gene expression, real time PCR) and protein levels (immunohistochemistry) were higher in ER-α-positive grade 1 EC than c...
61 citations
TL;DR: The brains of individuals with Alzheimer's disease (AD) and of animals in an AD mouse model exhibit abnormally elevated levels of 17β-HSD10, a homotetrameric mitochondrial multifunctional enzyme that catalyzes the oxidation of neuroactive steroids and the degradation of isoleucine.
61 citations
TL;DR: In the human prostate, UGT 2B15 and UGT2B17 genes have complementary roles, and are expressed in cells where their specific substrates are synthesized, which reinforces the hypothesis that UGT enzymes catalyze an important mechanism for modulating the action of steroids and protecting the steroid‐sensitive tissues from deleteriously high steroid concentrations.
Abstract: In humans, 3β‐hydroxysteroid dehydrogenase (3β‐HSD), 17β‐HSD, and 5α‐reductase enzymes convert dehydroepiandrosterone (DHEA), androstenedione, and testosterone into the most potent natural androgen dihydrotestosterone (DHT) in the prostate. This androgen is transformed mainly in situ to two Phase I metabolites, androsterone (ADT) and androstane‐3α,17β‐diol (3α‐DIOL), which can, however, be back‐converted to DHT. Here, we report recent findings on the characterization of specific anti‐UDP‐glucuronosyltransferases (UGT)2B15 and 2B17 antibodies and their use to identify UGT2B expressing‐cells in the human prostate epithelium. We found that UGT2B17 is expressed in basal cells where DHEA is converted into 3α‐DIOL and ADT. By contrast, the expression of UGT2B15 was observed only in luminal cells, where DHT is formed from testosterone. These results demonstrate that, in the human prostate, UGT2B15 and UGT2B17 genes have complementary roles, and are expressed in cells where their specific substrates are synthesiz...
61 citations