Evolution of 17beta-hydroxysteroid dehydrogenases and their role in androgen, estrogen and retinoid action.
17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) regulate androgen and estrogen concentrations in mammals. By 1995, four distinct enzymes with 17beta-HSD activity had been identified--17beta-HSD-types 1 and 3, which, in vivo, are NADPH-dependent reductases; and 17beta-HSD-types 2 and 4, which, in vivo, are NAD(+)-dependent oxidases. Since then, six additional enzymes with 17beta-HSD activity have been isolated from mammals. With the exception of 17beta-HSD-type 5, which belongs to the aldoketo-reductase (AKR) family, these 17beta-HSDs belong to the short chain dehydrogenase/reductase (SDR) family. Several 17beta-HSDs appear to be examples of convergent evolution. That is, 17beta-HSD activity arose several times from different ancestors. Some 17beta-HSDs share a common ancestor with retinoid oxido-reductases and have retinol dehydrogenase activity. 17beta-HSD-types 2, 6 and 9 appear to have diverged from ancestral retinoid dehydrogenases early in the evolution of deuterostomes during the Cambrian, about 540 million years ago. This coincided with the origin of nuclear receptors for androgens and estrogens suggesting that expression of 17beta-HSDs had an important role in the early evolution of the physiological response to androgens and estrogens.
Baker
M E
ME
Department of Medicine, 0823 University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0823, USA. mbaker@ucsd.edu
D042842:11-beta-Hydroxysteroid Dehydrogenases; D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D004967:Estrogens / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D010802:Phylogeny; D011944:Receptors, Androgen / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D012176:Retinoids / Q000378:metabolism*
D000728:Androgens; D004967:Estrogens; D007527:Isoenzymes; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012176:Retinoids; D009249:NADP; D015067:17-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases