title: Evolution of mammalian 11beta- and 17beta-hydroxysteroid dehydrogenases-type 2 and retinol dehydrogenases from ancestors in Caenorhabditis elegans and evidence for horizontal transfer of a eukaryote dehydrogenase to E. coli.
abstract: Physiological responses due to steroid hormones and retinoids are regulated by their cognate receptors and dehydrogenases. The origins of either regulatory mechanism are not fully understood. Here we examine the origins of the human 11beta-hydroxysteroid dehydrogenase-type 2, which regulates access of glucocorticoids to cells, and 17beta-hydroxysteroid dehydrogenase-type 2, which regulates access of androgens and estrogens to cells. Sequence comparisons trace their ancestry to homologs in Caenorhabditis elegans. These C. elegans proteins most closely resemble mammalian all-trans and 11-cis-retinol dehydrogenases. The similarity is sufficient -37% to 43% identity to suggest that one or more of the C. elegans homologs metabolizes a retinoid. Receptors for retinoids, but not for androgens, estrogens or glucocorticoids have been identified in C. elegans, suggesting that retinoid-mediated gene transcription is more ancient than that for adrenal and sex steroids. We propose that the hydroxysteroid dehydrogenase-type 2 mechanism for regulating the androgen, estrogen and glucocorticoid concentrations in mammals descended from that for regulating retinoid concentrations. Interestingly, E. coli contains a protein with strong sequence similarity to mammalian retinol dehydrogenases. Sequence comparisons and phylogenetic analysis indicate that the E. coli protein may be an example of horizontal transfer from a eukaryote ancestor.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0623, USA. mbaker@ucsd.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Baker
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000235:genetics; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D010802:Phylogeny; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; C113992:trans-retinol dehydrogenase; C022520:retinol dehydrogenase; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006884:Hydroxybutyrate Dehydrogenase; C504568:Cyp2d1 protein, rat; D000072467:Cytochrome P450 Family 2