  Cortisol, corticosterone and aldosterone activate full-length glucocorticoid
receptor (GR) from elephant shark, a cartilaginous fish belonging to the oldest
group of jawed vertebrates. Activation by aldosterone a mineralocorticoid,
indicates partial divergence of elephant shark GR from the MR. Progesterone
activates elephant shark MR, but not elephant shark GR. Progesterone inhibits
steroid binding to elephant shark GR, but not to human GR. Deletion of the
N-terminal domain (NTD) from elephant shark GR (Truncated GR) reduced the
response to corticosteroids, while truncated and full-length elephant shark MR
had similar responses to corticosteroids. Chimeras of elephant shark GR NTD
fused to MR DBD+LBD had increased activation by corticosteroids and
progesterone compared to full-length elephant shark MR. Elephant shark MR NTD
fused to GR DBD+LBD had similar activation as full-length elephant shark MR,
indicating that activation of human GR by the NTD evolved early in GR
divergence from the MR.
