2019/11/08 by Yoshinao Katsu, Katsu, Yoshinao, Shariful, Islam MD +12
Biochemistry, Genetics and Molecular Biology · Environmental Science · Medicine · #Biomolecules (q-bio.BM) #FOS: Biological sciences #Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities #Hormonal Regulation and Hypertension #Molecular Networks (q-bio.MN) #Physiological and biochemical adaptations
paper · pdf · doi:10.48550/arxiv.1911.03517
openalex publication_date 2019/11/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.