Expression cloning and characterization of oxidative 17β- and 3α- hydroxysteroid dehydrogenases from rat and human prostate

Michael G. Biswas, David W. Russell

Research output: Contribution to journalArticle

208 Scopus citations

Abstract

Intracellular levels of active steroid hormones are determined by their relative rates of synthesis and breakdown. In the case of the potent androgen dihydrotestosterone, synthesis from the precursor testosterone is mediated by steroid 5α-reductase, whereas breakdown to the inactive androgens 5α- androstane-3α,17β-diol (3α-adiol), and androsterone is mediated by reductive 3α-hydroxysteroid dehydrogenases (3α-HSD) and oxidative 17β- hydroxysteroid dehydrogenases (17β-HSD), respectively. We report the isolation by expression cloning of a cDNA encoding a 17β-HSD6 isozyme that oxidizes 3α-adiol to androsterone. 17β-HSD6 is a member of the short chain dehydrogenase/reductase family and shares 65% sequence identity with retinol dehydrogenase 1 (RoDH1), which catalyzes the oxidation of retinol to retinal. Expression of rat and human RoDH cDNAs in mammalian cells is associated with the oxidative conversion of 3α-adiol to dihydrotestosterone. Thus, 17β- HSD6 and RoDH play opposing roles in androgen action; 17β-HSD6 inactivates 3α-adiol by conversion to androsterone and RoDH activates 3α-adiol by conversion to dihydrotestosterone. The synthesis of an active steroid hormone by back conversion of an inactive metabolite represents a potentially important mechanism by which the steady state level of a transcriptional effector can be regulated.

Original languageEnglish (US)
Pages (from-to)15959-15966
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number25
DOIs
StatePublished - Jun 20 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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