title: Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar.
abstract: The response to a panel of steroids by the mineralocorticoid receptor (MR) from Amur sturgeon and tropical gar, two basal ray-finned fish, expressed in HEK293 cells was investigated. Half-maximal responses (EC50s) for transcriptional activation of sturgeon MR by 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol and aldosterone, and progesterone (Prog) were between 13 and 150 pM. For gar MR, EC50s were between 8 and 55 pM. Such low EC50s support physiological regulation by these steroids of the MR in sturgeon and gar. Companion studies with human and zebrafish MRs found higher EC50s compared with EC50s for sturgeon and gar MRs, with EC50s for zebrafish MR closer to gar and sturgeon MRs than was human MR. For zebrafish MR, EC50s were between 75 and 740 pM; for human MR, EC50s were between 65 pM and 2 nM. In addition to Prog, spironolactone (spiron) and 19nor-progesterone (19norP) were agonists for all three fish MRs, in contrast with their antagonist activity for human MR, which is hypothesized to involve serine-810 in human MR because all three steroids are agonists for a mutant human Ser810Leu-MR. Paradoxically, sturgeon, gar, and zebrafish MRs contain a serine corresponding to serine-810 in human MR. Our data suggest alternative mechanism(s) for Prog, spiron, and 19norP as MR agonists in these three ray-finned fishes and the need for caution in applying data for Prog signaling in zebrafish to human physiology.
authors: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors: Akira
authors: A
authors: Sugimoto
authors: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors: Kaori
authors: K
authors: Oka
authors: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors: Rui
authors: R
authors: Sato
authors: Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Japan.
authors: Shinji
authors: S
authors: Adachi
authors: Department of Medicine, University of California, San Diego, CA, USA.
authors: Michael E
authors: ME
authors: Baker
authors: Graduate School of Life Science, Hokkaido University, Sapporo, Japan Department of Biological Sciences, Hokkaido University, Sapporo, Japan.
authors: Yoshinao
authors: Y
authors: Katsu
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003350:Cortodoxone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D029941:Fish Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005399:Fishes; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D010802:Phylogeny; D011374:Progesterone / Q000494:pharmacology*; D018161:Receptors, Mineralocorticoid / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D029941:Fish Proteins; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone
keywords: Amur sturgeon; corticosteroids; mineralocorticoid evolution; mineralocorticoid receptor; progesterone; tropical gar