皮质类固醇、孕酮和螺内酯对象鲨盐皮质激素受体的转录激活作用
Transcriptional Activation of Elephant Shark Mineralocorticoid Receptor by Corticosteroids, Progesterone and Spironolactone
摘要：
我们报告的分析激活皮质类固醇和孕酮的全长盐皮质激素受体（MR）的象鲨，软骨鱼属于最古老的一组有颌脊椎动物。根据它们的活性测定，醛固酮、皮质醇、11-脱氧皮质酮、皮质酮、11-脱氧皮质醇、孕酮和19-去甲孕酮是潜在的生理性盐皮质激素。然而，醛固酮，生理盐皮质激素在人类和其他陆生脊椎动物，是没有发现软骨或鳍鱼。由于孕酮是激活象鲨MR的皮质类固醇的前体，我们提出孕酮是象鲨MR的祖先配体。虽然孕酮激活鳍鱼MR，但孕酮不激活人类，两栖动物或鳄鱼MR，这表明在向陆地脊椎动物过渡的过程中，孕酮失去了激活MR的能力。对象鲨MR与人MR的RNA序列分析的比较表明，MR在人脑、心脏、卵巢睾丸和其他非上皮组织在软骨鱼类中进化。总之，这些数据表明，胆固醇激活的MR可能在象鲨卵巢和睾丸中具有不受重视的功能。
英文摘要：
We report the analysis of activation by corticosteroids and progesterone of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. 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. Because progesterone is a precursor for corticosteroids that activate elephant shark MR, we propose that progesterone was an ancestral ligand for elephant shark MR. 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. Comparison of RNA-sequence analysis of elephant shark MR with that of human MR suggests that MR expression in the human brain, heart, ovary, testis and other non-epithelial tissues evolved in cartilaginous fishes. Together, these data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.
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