The Signalling Laboratory, The Babraham Institute, The Babraham Research Campus, Cambridge, CB22 3AT, UK.
Mol Cell Endocrinol. 2019 Oct 1;496:110537. doi: 10.1016/j.mce.2019.110537. Epub 2019 Aug 9.
The GPCR, GPER, mediates many of the rapid, non-genomic actions of 17β-estradiol in multiple tissues, including the nervous system. Controversially, it has also been suggested to be activated by aldosterone, and by the non-steroidal diphenylacrylamide compound, STX, in some preparations. Here, the ability of the GPER agonist, G-1, and aldosterone in the presence of the mineralocorticoid receptor antagonist, eplerenone, to potentiate forskolin-stimulated cyclic AMP levels in the hippocampal clonal cell line, mHippoE-18, are compared. Both stimulatory effects are blocked by the GPER antagonist G36, by PTX, (suggesting the involvement of Gi/o G proteins), by BAPTA-AM, (suggesting they are calcium sensitive), by wortmannin (suggesting an involvement of PI3Kinase) and by soluble amyloid-β peptides. STX also stimulates cyclic AMP levels in mHippoE-18 cells and these effects are blocked by G36 and PTX, as well as by amyloid-β peptides. This suggests that both aldosterone and STX may modulate GPER signalling in mHippoE-18 cells.
G 蛋白偶联受体（GPCR）、GPER 介导了 17β-雌二醇在包括神经系统在内的多种组织中的许多快速、非基因组作用。有争议的是，它也被认为被醛固酮和某些制剂中的非甾体二苯丙烯酰胺化合物 STX 激活。在这里，比较了 GPER 激动剂 G-1 和醛固酮在盐皮质激素受体拮抗剂依普利酮存在的情况下增强海马克隆细胞系 mHippoE-18 中 forskolin 刺激的环 AMP 水平的能力。这两种刺激作用都被 GPER 拮抗剂 G36、PTX（表明涉及 Gi/o G 蛋白）、BAPTA-AM（表明它们对钙敏感）、wortmannin（表明涉及 PI3K 激酶）和可溶性淀粉样蛋白-β肽阻断。STX 还刺激 mHippoE-18 细胞中环 AMP 水平，这些作用被 G36 和 PTX 以及淀粉样蛋白-β肽阻断。这表明醛固酮和 STX 都可能调节 mHippoE-18 细胞中的 GPER 信号。
