Hermidorff Milla Marques, de Assis Leonardo Vinícius Monteiro, Isoldi Mauro César
Laboratory of Hypertension, Research Center in Biological Science, Institute of Exact and Biological Sciences, Federal University of Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil.
Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Heart Fail Rev. 2017 Jan;22(1):65-89. doi: 10.1007/s10741-016-9591-2.
Aldosterone is the most known mineralocorticoid hormone synthesized by the adrenal cortex. The genomic pathway displayed by aldosterone is attributed to the mineralocorticoid receptor (MR) signaling. Even though the rapid effects displayed by aldosterone are long known, our knowledge regarding the receptor responsible for such event is still poor. It is intense that the debate whether the MR or another receptor-the "unknown receptor"-is the receptor responsible for the rapid effects of aldosterone. Recently, G protein-coupled estrogen receptor-1 (GPER-1) was elegantly shown to mediate some aldosterone-induced rapid effects in several tissues, a fact that strongly places GPER-1 as the unknown receptor. It has also been suggested that angiotensin receptor type 1 (AT1) also participates in the aldosterone-induced rapid effects. Despite this open question, the relevance of the beneficial effects of aldosterone is clear in the kidneys, colon, and CNS as aldosterone controls the important water reabsorption process; on the other hand, detrimental effects displayed by aldosterone have been reported in the cardiovascular system and in the kidneys. In this line, the MR antagonists are well-known drugs that display beneficial effects in patients with heart failure and hypertension; it has been proposed that MR antagonists could also play an important role in vascular disease, obesity, obesity-related hypertension, and metabolic syndrome. Taken altogether, our goal here was to (1) bring a historical perspective of both genomic and rapid effects of aldosterone in several tissues, and the receptors and signaling pathways involved in such processes; and (2) critically address the controversial points within the literature as regarding which receptor participates in the rapid pathway display by aldosterone.
醛固酮是肾上腺皮质合成的最为人熟知的盐皮质激素。醛固酮所展示的基因组途径归因于盐皮质激素受体（MR）信号传导。尽管醛固酮所表现出的快速效应早已为人所知，但我们对于负责此类效应的受体的了解仍然有限。关于是MR还是另一种受体——“未知受体”——是负责醛固酮快速效应的受体，这一争论十分激烈。最近，G蛋白偶联雌激素受体-1（GPER-1）已被确切证明可介导醛固酮在多个组织中引起的一些快速效应，这一事实有力地表明GPER-1就是那个未知受体。也有人提出1型血管紧张素受体（AT1）也参与醛固酮诱导的快速效应。尽管存在这个尚未解决的问题，但醛固酮有益效应的相关性在肾脏、结肠和中枢神经系统中是明确的，因为醛固酮控制着重要的水重吸收过程；另一方面，醛固酮在心血管系统和肾脏中所表现出的有害效应也已有报道。就此而言，MR拮抗剂是众所周知的药物，在心力衰竭和高血压患者中显示出有益效果；有人提出MR拮抗剂在血管疾病、肥胖、肥胖相关高血压和代谢综合征中也可能发挥重要作用。综上所述，我们这里的目标是：（1）对醛固酮在多个组织中的基因组效应和快速效应，以及参与这些过程的受体和信号通路进行历史回顾；（2）批判性地探讨文献中关于哪种受体参与醛固酮所展示的快速途径这一有争议的问题。
