PT - JOURNAL ARTICLE AU - Yoshinao Katsu AU - Satomi Kohno AU - Kaori Oka AU - Xiaozhi Lin AU - Sumika Otake AU - Nisha E. Pillai AU - Wataru Takagi AU - Susumu Hyodo AU - Byrappa Venkatesh AU - Michael E. Baker TI - Transcriptional Activation of Elephant Shark Mineralocorticoid Receptor by Corticosteroids, Progesterone and Spironolactone AID - 10.1101/265348 DP - 2018 Jan 01 TA - bioRxiv PG - 265348 4099 - http://biorxiv.org/content/early/2018/12/06/265348.short 4100 - http://biorxiv.org/content/early/2018/12/06/265348.full AB - We report the analysis of activation of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates by corticosteroids and progesterone. Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes. Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Both elephant shark MR and human MR are expressed in the brain, heart, ovary, testis and other non-epithelial tissues, indicating that MR expression in diverse tissues evolved in the common ancestor of jawed vertebrates. Our data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.