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

17 beta -Hydroxysteroid dehydrogenases (17 beta -HSDs) regulate androgen and estrogen concentrations in mammals. By 1995, four distinct enzymes with 17 beta -HSD activity had been identified - 17 beta -HSD-types 1 and 3, which, 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 the 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 convergent evolution. That is, 17 beta -HSD activity arose several times from different ancestors. Some 17 beta -HSDs share a common ancestor with retinoid oxido-reductases and have retinol dehydrogenase activity. 17 beta -HSD-types 2. 6 and 9 appear to have diverged from ancestral retinoid dehydrogenases early in the evolution or deuterostomes during the Cambrian, about 540 million years ago. This coincided with the origin of nuclear receptors for androgens and estrogens suggesting th;lt expression of 17 beta -HSDs had an important role in the early evolution of the physiological response to androgens and estrogens. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.