TY - JOUR
T1 - Tissue distribution and kinetic characteristics of rat steroid 5α-reductase isozymes
T2 - Evidence for distinct physiological functions
AU - Normington, Karl
AU - Russell, David W.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1992/9/25
Y1 - 1992/9/25
N2 - 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.
AB - 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.
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M3 - Article
C2 - 1527072
AN - SCOPUS:0026723090
SN - 0021-9258
VL - 267
SP - 19548
EP - 19554
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 27
ER -