Interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol in rat kidney: heterogeneity of 3alpha-hydroxysteroid oxidoreductases.
3alpha-Hydroxysteroid oxidoreductases catalyzing the interconversion between 17 beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone) and 5alpha-androstane-3alpha, 17 beta-diol (3alpha-androstanediol) have been studied in rat kidney. Three enzymes can be distinguished: a soluble NADPH-dependent oxidoreductase, a microsomal NADPH-dependent enzyme and a microsomal NADH-linked enzyme. Traces of the microsomal enzymes are consistently observed in the 108 000 X g supernatant. Studies on crude preparations reveal that these enzymes differ not only in subcellular localization and co-factor requirement, but also in optimum pH, kinetic characteristics, sensitivity to potential steroidal inhibitors and sensitivity to detergents, ionic strength and temperature. Moreover, salient sex differences exist in the activity of all three kidney enzymes. The soluble NADPH-dependent enzyme is more active in female rats whereas both microsomal enzymes are considerably more active in male animals. The microsomal NADH-dependent oxidoreductase displays favorable characteristics to catalyze the 3alpha-dehydrogenation of 3alpha-androstanediol. Evidence is presented that it is mainly this enzyme that enables the kidney to use 3alpha-androstanediol as an efficient precursor for the local formation of 5alpha-dihydrotestosterone.
D015113:Androstane-3,17-diol / Q000378:metabolism*; D000731:Androstanes / Q000378:metabolism*; D000818:Animals; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009994:Osmolar Concentration; D010710:Phosphates; D051381:Rats; D012737:Sex Factors; D013696:Temperature
D000731:Androstanes; D010710:Phosphates; D013196:Dihydrotestosterone; D009243:NAD; D015113:Androstane-3,17-diol; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases