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 a Cartilaginous Fish (Elephant Shark, <em>Callorhinchus milii</em>) Mineralocorticoid Receptor by Corticosteroids, Progestins and Spironolactone
AID  - 10.1101/265348
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 265348
4099  - http://biorxiv.org/content/early/2018/02/13/265348.short
4100  - http://biorxiv.org/content/early/2018/02/13/265348.full
AB  - A distinct mineralocorticoid receptor (MR) first appears in cartilaginous fishes (Chondrichthyes), the oldest group of extant jawed vertebrates. To investigate steroid specificity of cartilaginous fish MR, we studied transcriptional activation of full-length elephant shark (Callorhinchus milii) MR by aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone. All investigated corticosteroids and progestins showed half-maximal responses (EC50s) below 1 nM for elephant shark MR, and hence are potential physiological mineralocorticoids. Progesterone and 19-norprogesterone are antagonists for human, Xenopus and alligator MRs, but agonists for ray-finned fish and chicken MRs, indicating that MR activation by progestins is an ancestral response, conserved in ray-finned fish, lost in Xenopus, alligator and human, and distinct from chicken MR activation, which arose independently. RNA-seq analysis finds strong MR expression in elephant shark ovary and testis, in which progesterone-activated MR may have novel functions.