Evolution of 17 beta-hydroxysteroid dehydrogenases and their role in androgen, estrogen and retinoid action

17 beta -Hydroxysteroid dehydrogenases (17 beta -HSDs) regulate androgen an d estrogen concentrations in mammals. By 1995, four distinct enzymes with 1 7 beta -HSD activity had been identified - 17 beta -HSD-types 1 and 3, whic h, in vivo, are NADPH-dependent reductases: and 17 beta -HSD-types 2 and 4. which, in vivo, are NAD(+)-dependent oxidases. Since then, six additional enzymes with 17 beta -HSD activity have been isolated from mammals. With th e exception of 17 beta -HSD-type 5, which belongs to the aldoketo-reductase (AKR) family, these 17 beta -HSDs belong to the short chain dehydrogenase/ reductase (SDR) Family. Several 17 beta -HSDs appear to be examples of conv ergent evolution. That is, 17 beta -HSD activity arose several times from d ifferent ancestors. Some 17 beta -HSDs share a common ancestor with retinoi d oxido-reductases and have retinol dehydrogenase activity. 17 beta -HSD-ty pes 2. 6 and 9 appear to have diverged from ancestral retinoid dehydrogenas es early in the evolution or deuterostomes during the Cambrian, about 540 m illion years ago. This coincided with the origin of nuclear receptors for a ndrogens and estrogens suggesting th;lt expression of 17 beta -HSDs had an important role in the early evolution of the physiological response to andr ogens and estrogens. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.