Normington K, Russell D W
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
J Biol Chem. 1992 Sep 25;267(27):19548-54.
The enzyme steroid 5 alpha-reductase (5 alpha-reductase) catalyzes the reduction of delta 4,5 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 5 alpha-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-5 alpha-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 5 alpha-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 5 alpha-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.
类固醇5α-还原酶（5α-还原酶）可催化多种底物中δ4,5双键的还原反应，被认为在类固醇激素代谢中兼具分解代谢和合成代谢作用。在此，我们描述了大鼠5α-还原酶2型同工酶编码cDNA的分离与特性鉴定，并将该同工酶与1型同工酶的动力学特性及组织特异性表达模式进行了比较。2型同工酶对类固醇底物的表观Km值在纳摩尔范围内，而1型同工酶的亲和力为微摩尔级。两种同工酶对各种4-氮杂甾体的抑制作用不同，2型同工酶对21,21-亚戊基-4-氮杂-5α-孕甾-1-烯-3,20-二酮表现出极高的敏感性（Ki = 40 pM）。在大多数雄性生殖组织中，编码2型同工酶的信使RNA比1型信使RNA更为丰富，而在周围组织中1型信使RNA占主导。在再生前列腺中，5α-还原酶的两种信使RNA被双氢睾酮诱导的效率均高于睾酮。5α-还原酶同工酶在底物亲和力和组织分布上的差异表明，2型同工酶在雄激素及其他类固醇激素代谢中起合成代谢作用，而1型同工酶起分解代谢作用。
