Evolution of steroid-5alpha-reductases and comparison of their function with 5beta-reductase.

Steroid-5alpha-reductases (SRD5alpha) and steroid-5beta-reductase (SRD5beta) represent a convergence in evolution: they share similar biological functions, but do not have a common ancestor. In vertebrates, SRD5alpha and SRD5beta are involved in C-19 and C-21 steroid biosynthesis, bile acid biosynthesis and erythropoiesis. We compare and contrast the history, evolution, tissue distribution, enzyme characteristics and biological functions of SRD5alpha and SRD5beta and suggest possible future directions for research efforts. Both, the unique and overlapping roles that SRD5alpha and SRD5beta play in steroid hormone metabolism, are indicated. We also present the phylogeny of the SRD5alpha. The main SRD5alpha subfamilies obtained include, not only the well-known SRD5alpha type 1, type 2 and type 3, but also the synaptic glycoprotein (GPSN2)/trans-2,3-enoly-CoA reductase group. Phylogenetic analysis indicated that a eukaryotic ancestor likely underwent duplication events to generate these three subfamilies (type 1/2, type 3 and GPSN2 ancestors); both SRD5alpha type 1/2 and GPSN2 subfamilies may have evolved by ancient duplication events at the early stage of vertebrate and chordate evolution. Copyright 2009 Elsevier Inc. All rights reserved.