RT Journal Article
SR Electronic
T1 Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 053199
DO 10.1101/053199
A1 Akira Sugimoto
A1 Kaori Oka
A1 Rui Sato
A1 Shinji Adachi
A1 Michael E. Baker
A1 Yoshinao Katsu
YR 2016
UL http://biorxiv.org/content/early/2016/07/29/053199.abstract
AB 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 were between 13 pM and 150 pM. For gar MR, EC50s were between 8 pM and 55 pM. Such low EC50s support physiological regulation by these steroids of the MR in sturgeon and gar. Companion studies with human MR and zebrafish MR found higher EC50s compared to EC50s for sturgeon and gar MR, with EC50s for zebrafish MR closer to gar and sturgeon MR than was human MR. For zebrafish MR, EC50s were between 75 pM and 740 pM; for human MR, EC50s were between 65 pM and 2 nM. In addition to progesterone, spironolactone and 19nor-progesterone were agonists for all three fish MRs, in contrast to 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 suggests alternative mechanism(s) for progesterone, spironolactone and 19nor-progesterone as MR agonists in these three ray-finned fishes and the need for caution in applying data for progesterone signaling in zebrafish to human physiology.