Mechanisms of ligand-mediated modulation of mineralocorticoid receptor signaling

The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism. This review will discuss the current understanding, including recent insights into these interactions, with implications for an emerging array of novel non-steroidal compounds targeting the mineralocorticoid receptor; and highlight their relevance to ligand- or tissue-specificity as well as their suitability as therapeutic agents.