The mouse 3 beta-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins.
The enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) plays an essential role in the biosynthesis of all steroid hormones. We previously reported the isolation, characterization, and tissue-specific expression of four distinct but highly homologous 3 beta HSD cDNAs (forms I, II, III, and IV). Enzymatic characterization of three of these isoforms demonstrated that mouse 3 beta HSD I and III function as dehydrogenase/isomerases, but 3 beta HSD IV functions exclusively as a 3-ketosteroid reductase. We now report the isolation and characterization of an additional distinct mouse 3 beta HSD cDNA, 3 beta HSD V, which is expressed in the liver of male mice beginning in late puberty. Similar to 3 beta HSD IV, 3 beta HSD V functions exclusively as a 3-ketosteroid reductase converting an active androgen, dihydrotestosterone (DHT), into an inactive androgen, 5 alpha-androstane-3 beta,17 beta-diol. Expressed 3 beta HSD V, however, exhibits a considerably lower apparent Michaelis-Menten constant (Km) value for DHT than 3 beta HSD IV (0.47 microM vs. 2.2 microM, respectively). The complete predicted amino acid sequence of 3 beta HSD II is also reported. The predicted amino acid sequence of mouse 3 beta HSD V reveals that this new form is more closely related to the 3-ketosteroid reductases, mouse 3 beta HSD IV and rat III (93 and 84% identity, respectively), than to the other rodent isoforms that share less than 75% identity.(ABSTRACT TRUNCATED AT 250 WORDS)
D015096:3-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D013196:Dihydrotestosterone / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D005810:Multigene Family; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D051381:Rats; D012741:Sexual Maturation; D013379:Substrate Specificity; D014162:Transfection
D018076:DNA, Complementary; D013196:Dihydrotestosterone; D009243:NAD; D009249:NADP; D015096:3-Hydroxysteroid Dehydrogenases