Title: N-terminal domain Increases Activation of Elephant Shark Glucocorticoid and Mineralocorticoid Receptors Show Chinese title

Title: N端结构域增强象鲨糖皮质激素和盐皮质激素受体的激活

Abstract: 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. Show Chinese abstract

Abstract: 皮质醇、皮质酮和醛固酮激活来自象鲨的全长糖皮质激素受体（GR），象鲨是一种属于最古老有颌脊椎动物群体的软骨鱼类。 醛固酮（一种盐皮质激素）的激活表明象鲨GR与MR部分分化。孕酮激活象鲨MR，但不激活象鲨GR。 孕酮抑制象鲨GR的类固醇结合，但不抑制人GR的类固醇结合。 从象鲨GR中删除N端结构域（NTD）（截断GR）降低了对皮质类固醇的反应，而截断和全长象鲨MR对皮质类固醇的反应相似。 将象鲨GR NTD与MR DBD+LBD融合的嵌合体比全长象鲨MR对皮质类固醇和孕酮的激活作用增强。 将象鲨MR NTD与GR DBD+LBD融合的嵌合体的激活作用与全长象鲨MR相似，表明人类GR的NTD激活作用在GR与MR分化早期就已出现。