title: 3 Alpha-hydroxysteroid oxidoreductase activities in dihydrotestosterone degradation and back-formation in rat prostate and epididymis.
abstract: The metabolism of dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) was assessed in full homogenates of rat prostate and epididymis. The major degradational route of DHT was catalysed by the enzyme(s) 3 alpha-hydroxysteroid oxidoreductase (HSOR). Enzyme kinetic characteristics Vmax, Km and Vmax/Km ratio, were obtained for the NADP(H)- and NAD(H)-dependent interconversion of DHT and 3 alpha-Adiol at pH 7.0 and at saturated co-factor concentration. For both the reduction of DHT and the oxidation of 3 alpha-Adiol, NAD(H) was the preferred co-factor when activities were rated by their Vmax and Vmax/Km ratio. Combining the data with the earlier established Vmax/Km ratios for the 5 alpha-reductase isozyme type I and II activities in rat prostate and epididymis indicated that DHT, at saturated co-factor concentrations, would not be sustained in either tissue considering the reported enzyme characteristics. The reported exclusive bioavailability of the co-factors NADPH and NAD+ in vivo, however, will direct the metabolic pathways in these tissues to sustain the formation of DHT.
authors.affiliation: Department of Medicine, University Hospital, Nijmegen, The Netherlands.
authors.forename: P N
authors.initials: PN
authors.lastname: Span
authors.forename: C G
authors.initials: CG
authors.lastname: Sweep
authors.forename: T J
authors.initials: TJ
authors.lastname: Benraad
authors.forename: A G
authors.initials: AG
authors.lastname: Smals
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism*; D004789:Enzyme Activation; D004822:Epididymis / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D013196:Dihydrotestosterone; D009243:NAD; D009249:NADP; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)