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

346 Citations (Scopus)

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 Km 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 (Ki = 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 - Sep 25 1992

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Tissue Distribution
Isoenzymes
Rats
Oxidoreductases
Steroids
Tissue
Kinetics
Steroid hormones
Messenger RNA
Metabolism
Azasteroids
Substrates
Hormones
Dihydrotestosterone
Androgens
Testosterone
Prostate
Complementary DNA
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tissue distribution and kinetic characteristics of rat steroid 5α-reductase isozymes : Evidence for distinct physiological functions. / Normington, Karl; Russell, David W.

In: Journal of Biological Chemistry, Vol. 267, No. 27, 25.09.1992, p. 19548-19554.

Research output: Contribution to journalArticle

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