The mouse 3 beta-hydroxysteroid dehydrogenase multigene family includes two functionally distinct groups of proteins

Mol Endocrinol. 1995 Sep;9(9):1214-22. doi: 10.1210/mend.9.9.7491113.

Abstract

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)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / chemistry
  • 3-Hydroxysteroid Dehydrogenases / genetics*
  • 3-Hydroxysteroid Dehydrogenases / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • Dihydrotestosterone / metabolism
  • Kinetics
  • Liver / growth & development
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Multigene Family*
  • NAD / pharmacology
  • NADP / pharmacology
  • Rats
  • Sexual Maturation
  • Substrate Specificity
  • Transfection

Substances

  • DNA, Complementary
  • Dihydrotestosterone
  • NAD
  • NADP
  • 3-Hydroxysteroid Dehydrogenases

Associated data

  • GENBANK/L41519