2021/06/26 by Yoshinao Katsu, Katsu, Yoshinao, Shin Oana +7
Environmental Science · Biochemistry, Genetics and Molecular Biology · Medicine · #Physiological and biochemical adaptations #Reproductive biology and impacts on aquatic species #Hormonal Regulation and Hypertension
paper · pdf · doi:10.48550/arxiv.2106.14114
Aldosterone, the main physiological mineralocorticoid in humans and other\nterrestrial vertebrates, first appears in lungfish, which are lobe-finned fish\nthat are forerunners of terrestrial vertebrates. Aldosterone activation of the\nMR regulates internal homeostasis of water, sodium and potassium, which was\ncritical in the conquest of land by vertebrates. We studied transcriptional\nactivation of the slender African lungfish MR by aldosterone, other\ncorticosteroids and progesterone and find that aldosterone,\n11-deoxycorticosterone, 11-deoxycortisol and progesterone have half-maximal\nresponses (EC50s) below 1 nM and are potential physiological\nmineralocorticoids. In contrast, EC50s for corticosterone and cortisol were 23\nnM and 66 nM, respectively. Unexpectedly, truncated lungfish MR, consisting of\nthe DNA-binding, hinge and steroid-binding domains, had a stronger response to\ncorticosteroids and progesterone than full-length lungfish MR, indicating that\nthe N-terminal domain represses steroid activation of lungfish MR, unlike human\nMR in which the N-terminal domain contains an activation function. BLAST\nsearches of GenBank did not retrieve a GR ortholog, leading us to test\ndexamethasone and triamcinolone for activation of lungfish MR. At 10 nM, both\nsynthetic glucocorticoids are about 4-fold stronger than 10 nM aldosterone in\nactivating full-length lungfish MR, leading us to propose that lungfish MR also\nfunctions as a GR.\n