Marzolla Vincenzo, Armani Andrea, Feraco Alessandra, De Martino Massimo U, Fabbri Andrea, Rosano Giuseppe, Caprio Massimiliano
Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Pisana, Rome, Italy.
Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy.
Steroids. 2014 Dec;91:46-53. doi: 10.1016/j.steroids.2014.05.001. Epub 2014 May 10.
Aldosterone is the primary ligand for the mineralocorticoid receptor (MR) and has been considered long time a "renal" hormone, acting at this site as a key regulator of plasma volume, electrolyte homeostasis and blood pressure. A new exciting era of MR biology began with the identification of MR in different non-epithelial tissues such as brain, heart, vessels, macrophages/monocytes, and adipose tissue. The distribution of MR in such a wide range of tissues has suggested novel and unexpected roles for MR, for example in energy metabolism and inflammation. An increasing body of evidence suggests a detrimental effect of aldosterone excess on the development of metabolic alterations. Disturbances in glucose metabolism due to inappropriate activation of MR are frequently observed in patients with primary aldosteronism as well as in obese subjects. MR antagonists have beneficial effects on glucose tolerance and metabolic parameters in experimental animals, whereas their role in humans remains unclear. The aim of this review is to discuss the pathophysiology of MR activation in experimental models, particularly at the level of adipocytes and macrophages, to discuss novel and sometimes contrasting insights from emerging studies, and to highlight deficiencies in the field.
醛固酮是盐皮质激素受体(MR)的主要配体,长期以来一直被视为一种“肾脏”激素,在该部位作为血浆容量、电解质稳态和血压的关键调节因子发挥作用。随着在不同非上皮组织(如脑、心脏、血管、巨噬细胞/单核细胞和脂肪组织)中发现MR,MR生物学开启了一个令人兴奋的新时代。MR在如此广泛的组织中的分布表明其具有新的、意想不到的作用,例如在能量代谢和炎症方面。越来越多的证据表明醛固酮过多对代谢改变的发展具有有害影响。在原发性醛固酮增多症患者以及肥胖受试者中经常观察到由于MR不适当激活导致的葡萄糖代谢紊乱。MR拮抗剂对实验动物的葡萄糖耐量和代谢参数具有有益作用,但其在人类中的作用仍不清楚。本综述的目的是讨论实验模型中MR激活的病理生理学,特别是在脂肪细胞和巨噬细胞水平,讨论新兴研究中新颖的、有时相互矛盾的见解,并突出该领域的不足之处。