Molecular and cellular determinants of mineralocorticoid selectivity

Aldosterone plays a major role in the regulation of renal sodium reabsorption, of extracellular fluid volume and blood pressure. Such specific mineralocorticoid physiological adaptations occur despite the large prevalence of glucocorticoid hormones over aldosterone in the plasma. Indeed both classes of hormones bind with the same affinity to the mineralocorticoid receptor, but several mechanisms allow selective and tissue-specific aldosterone effects. They represent a series of mutually interacting selectivity filters, which have not yet been fully documented. The main determinants of aldosterone selective effects include an enzymatic protection of the mineralocorticoid receptor, the intrinsic properties of the mineralocorticoid receptor towards different ligands, and numerous possibilities of interaction between corticosteroid receptors (forming different homo or heterodimers) and other transcription factors.