Research Service, G. V. (Sonny) Montgomery VA Medical Center and University of Mississippi Medical Center, Jackson, MS 39216, USA.
Exp Physiol. 2010 Jan;95(1):13-8. doi: 10.1113/expphysiol.2008.045914. Epub 2009 Jul 31.
The mineralocorticoid receptor (MR) has been called a promiscuous receptor because its intrinsic affinity for aldosterone, cortisol and corticosterone is similar. Since glucocorticoids circulate in concentrations 100- to 1000-fold those of aldosterone, stoichiometry dictates that MR should be activated by glucocorticoids, not aldosterone, yet MRs are expressed in many tissues and regulate diverse functions, many of them under the regulation of the renin-angiotensin-aldosterone system. A relatively small number of brain MRs are aldosterone selective and modulate blood pressure. Evidence for possible mechanisms conferring ligand specificity in the context of mineralocorticoid-induced hypertension and the brain are discussed. These include factors (or mechanisms) intrinsic to the receptor, such as alternative splice variants and translation start sites, and extrinsic to the MR, including differential access through the blood-brain barrier, differential recruitment of co-regulators and scaffolding proteins, 11beta-steroid dehydrogenase activity, synthesis of potent acylated aldosterone derivatives and the synthesis of relevant amounts of aldosterone in areas of the brain that modulate blood pressure.
盐皮质激素受体（MR）被称为混杂受体，因为它对醛固酮、皮质醇和皮质酮的固有亲和力相似。由于糖皮质激素在循环中的浓度是醛固酮的 100-1000 倍，根据化学计量学，MR 应该被糖皮质激素激活，而不是醛固酮，但 MR 存在于许多组织中，并调节多种功能，其中许多功能受肾素-血管紧张素-醛固酮系统的调节。相对较少的脑 MR 是醛固酮选择性的，调节血压。讨论了在醛固酮诱导的高血压和大脑中赋予配体特异性的可能机制的证据。这些包括受体内在的因素（或机制），如选择性剪接变体和翻译起始位点，以及受体外在的因素，包括通过血脑屏障的差异进入、共调节剂和支架蛋白的差异募集、11β-类固醇脱氢酶活性、合成有效的酰化醛固酮衍生物以及在调节血压的大脑区域合成相关量的醛固酮。
