The mineralocorticoid receptor: A journey exploring its diversity and specificity of action

The mineralocorticoid receptor (MR) integrates hormonal signaling and activates the expression of aldosterone target genes, which control various physiological processes. In recent years, evidence has been provided for an important role of MR not only in the regulation of sodium and water homeostasis but also in cardiovascular function, neuronal fate, and adipocyte differentiation. MR belongs to the steroid receptor family that displays common mechanism of action. As a result, some apparent similarities with the glucocorticoid receptor (GR) have shaded MR's own specificities. The description of its gene structure, messenger isoforms, protein variants, functional domains, and posttranslational modifications ( phosphorylation, ubiquitinylation, sumoylation, acetylation) as well as a panel of interactions with coregulators, progressively depicted an original portrait of MR and shed light on its specific mechanism of action. In this review, after an overview of MR characteristics, the multiple levels of MR selectivity over other steroid receptors, in particular GR, will be described as well as the consequences for aldosterone-regulated gene expression.