Abstract
Abstract11[beta]-hydroxysteroid dehydrogenase type-2 (11[beta]-HSD2) regulates the local concentration of cortisol that can activate the glucocorticoid receptor and mineralocorticoid receptor, as well as the concentration of 11-keto-testosterone, the active androgen in fish. Similarly, 17[beta]-HSD2 regulates the levels of testosterone and estradiol that activate the androgen receptor and estrogen receptor, respectively. Interestingly, although human 11[beta]-HSD2 and 17[beta]-HSD2 act at different positions on different steroids, these enzymes are paralogs. Despite the physiological importance of 11[beta]-HSD2 and 17[beta]-HSD2, details of their origins and divergence from a common ancestor are not known. An opportunity to understand their evolution is presented by the recent sequencing of genomes from sea urchin, a basal deuterostome, and amphioxus, a basal chordate, and the availability of substantial sequence for acorn worm and elephant shark, which together provide a more complete dataset for analysis of the origins of 11[beta]-HSD2 and 17[beta]-HSD2. BLAST searches find an ancestral sequence of 17[beta]-HSD2 in sea urchin, acorn worm and amphioxus, while an ancestral sequence of 11[beta]-HSD2 first appears in sharks. Sequence analyses indicate that 17[beta]-HSD2 in sea urchin may have a non-enzymatic activity. Evolutionary analyses indicate that if acorn worm 17[beta]-HSD2 is catalytically active, then it metabolizes novel substrate(s).
Highlights
11 -hydroxysteroid dehydrogenase type-2 (11 -HSD2) and 17 -HSD2 catalyze the conversion of C11 and C17 alcohols, respectively, to ketones on glucocorticoids, androgens and estrogens [Figure 1], which makes these enzymes important partners with steroid receptors in the regulation of steroid hormone action [1,2,3,4]
We searched GenBank and other databases with 11 -HSD2 and 17 -HSD2 for orthologs. These searches found an ortholog of 17 -HSD2 in sea urchin, acorn worm and amphioxus, while 11 -HSD2 first appears in the elephant shark
BLAST searches show that 11 -HSD2 and 17 -HSD2 are closest to each other in GenBank
Summary
11 -hydroxysteroid dehydrogenase type-2 (11 -HSD2) and 17 -HSD2 catalyze the conversion of C11 and C17 alcohols, respectively, to ketones on glucocorticoids, androgens and estrogens [Figure 1], which makes these enzymes important partners with steroid receptors in the regulation of steroid hormone action [1,2,3,4]. 17 -HSD2 allows these enzymes to act as gatekeepers in regulating access of active glucocorticoids, androgens and estrogens to their receptors. Several questions remain regarding more ancient events in the evolution of 11 -HSD2 and 17 -HSD2 When did these enzymes evolve; which enzyme evolved first, and when did the second enzyme first appear in animals? These searches found an ortholog of 17 -HSD2 in sea urchin, acorn worm and amphioxus, while 11 -HSD2 first appears in the elephant shark This indicates that 17 -HSD2 is the ancestor of 11 -HSD2 and suggests that 17 -HSD2 and 11 -HSD2, respectively, may have had a role in evolution of basal deuterostomes [22] and sharks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
