Tissue distribution and kinetic characteristics of rat steroid 5α- reductase isozymes. Evidence for distinct physiological functions

Karl Normington, David W. Russell

Research output: Contribution to journalArticle

351 Scopus citations

Abstract

The enzyme steroid 5α-reductase (5α-reductase) catalyzes the reduction of Δ4,5 double bonds in a variety of substrates and is thought to play both catabolic and anabolic roles in steroid hormone metabolism. Here, we describe the isolation and characterization of a cDNA encoding the rat type 2 isozyme of 5α-reductase and compare the kinetic properties and tissue- specific expression patterns of this isozyme with those of the type 1 isozyme. The type 2 isozyme has apparent K(m) values in the nanomolar range for steroid substrates, whereas the type 1 isozyme has micromolar affinities. The isozymes differ in their inhibition by various 4-azasteroids with the type 2 isozyme showing exquisite sensitivity (K(i) = 40 pM) to 21,21- pentamethylene-4-aza-5α-pregn-1-ene-3,20-dione. Messenger RNAs encoding the type 2 isozyme are more abundant than type 1 mRNAs in most male reproductive tissues, whereas the type 1 mRNAs predominate in peripheral tissues. Both 5α-reductase mRNAs are more efficiently induced by dihydrotestosterone than by testosterone in the regenerating prostate. The differences in substrate affinities and tissue distributions of the 5α-reductase isozymes suggest that type 2 plays an anabolic role and type 1 a catabolic role in the metabolism of androgens and other steroid hormones.

Original languageEnglish (US)
Pages (from-to)19548-19554
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number27
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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