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: Compared (+)- and (-)-gossypols in the inhibition of 3beta-hydroxysteroid dehydrogenase and 17beta-HSD isoform 3 in human and rat testes, gossypol enantiomers competitively inhibited both 3beta -HSD and 17 beta- HSD3 by competing for the cofactor binding sites of these enzymes.
49 citations
TL;DR: Tissue distribution of mRNA encoding both types 1 and 3 17betaHSD was studied using reverse transcription and the polymerase chain reaction (RT-PCR).
48 citations
TL;DR: KLF15 is potentially a novel link between the regulation of testosterone production and fat stores by insulin in humans and its potential role in the pathogenesis of hyperandrogenism is presented.
Abstract: Context: Kruppel-like factor 15 (KLF15) is a newly discovered transcription factor that plays an important role in glucose homeostasis and lipid accumulation in cells. We present evidence for KLF15 as a transcriptional regulator of the human 17β-hydroxysteroid dehydrogenase type 5 gene (HSD17B5) and its potential role in the pathogenesis of hyperandrogenism. Objective: The aim was to investigate the molecular mechanism of HSD17B5 regulation. Methods: Diverse molecular biology techniques were used. Design and Results: We identified a KLF15 binding site in the HSD17B5 promoter by using luciferase promoter constructs, EMSA, and chromatin immunoprecipitation assays. Overexpression of KLF15 increased HSD17B5 promoter activity and testosterone formation at least 3-fold in cultured H295R cells. Insulin increased KLF15 mRNA expression according to real-time RT-PCR and increased HSD17B5 promoter activity according to luciferase assays. KLF15 overexpression in combination with insulin, glucocorticoid, and cAMP stim...
48 citations
TL;DR: An overview of the application of kinetic methods to the delineation of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) heterogeneity in mammalian tissues is presented, and analysis of human ovary indicates granulosa cells are particularly enriched in the type 1 enzyme with type 2-like activity in stroma/theca.
48 citations
TL;DR: Substrate specificity and cofactor requirement patterns as well as pH optima and kinetic properties suggest the occurrence of 17β‐HSD type 3 and type 4 in the human temporal lobe.
Abstract: Sex steroids exert important effects on the central nervous system (CNS). Although the formation of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) metabolites in the CNS was discovered almost 30 years ago, conclusive studies concerning 17beta-HSD activity in the human brain are still lacking. Therefore, we investigated 17beta-HSD in vitro activity in human temporal lobe biopsies of 13 women and 13 men using radioactively labelled androstenedione, testosterone, oestrone and 17beta-oestradiol and compared it to that in human placenta, liver, testis and prostate. We could demonstrate androgenic and oestrogenic 17beta-HSD activities in all tissues under investigation. The reduction of androstenedione and oestrone in brain was NADPH dependent with a broad pH optimum between 6.5 and 9.0, whereas the oxidation of testosterone and 17beta-oestradiol was NAD dependent with a pH optimum of >/=9.0. Using optimum cofactors sex differences of brain 17beta-HSD activities were not observed. Conversion of androstenedione, testosterone, oestrone and 17beta-oestradiol was significantly higher in the subcortical white matter than in the cerebral cortex. We could demonstrate a significant formation of testosterone in the brain tissue of all patients under investigation. Substrate specificity and cofactor requirement patterns as well as pH optima and kinetic properties suggest the occurrence of 17beta-HSD type 3 and type 4 in the human temporal lobe.
48 citations