Evolution of 11[beta]-Hydroxysteroid Dehydrogenase-Type 1 and 11[beta]-Hydroxysteroid Dehydrogenase-type 3

A key regulator of glucocorticoid action is 11[beta]-hydroxysteroid dehydrogenase type-1 (11[beta]-HSD1), which catalyzes the conversion of cortisone to cortisol, the biologically active glucocorticoid. 11[beta]-HSD1 is a paralog of 11[beta]-HSD3, whose physiological function remains unclear. As reported here, 11[beta]-HSD3 has orthologs in sea urchin, amphioxus and Ciona, while 11[beta]-HSD1 first appears in sharks. Thus, 11[beta]HSD3 arose before the evolution of glucocorticoid signaling, suggesting different ancestral function(s) for 11[beta]-HSD3. Four perplexing findings arise from this evolutionary analysis: 1) 11[beta]-HSD1 is not present in a ray-finned fish genome, 2) zebrafish and fathead minnow contain two isoforms of 11[beta]-HSD3; 3) neither rat nor mouse contain 11[beta]-HSD3 and 4) amphioxus contains sixteen 11[beta]-HSD3 paralogs.