Multiple aspects of mineralocorticoid selectivity

Aldosterone regulates renal sodium reabsorption through binding to the mine ralocorticoid receptor (MR). Because the glucocorticoid receptor (GR) is ex pressed together with the MR in aldosterone target cells, glucocorticoid ho rmones bound to GR may also intervene to modulate physiological functions i n these cells. In addition, each steroid can bind both receptors, and the M R has equal affinity for aldosterone and glucocorticoid hormones. Several c ellular and molecular mechanisms intervene to allow specific aldosterone re gulatory effects, despite the large prevalence of glucocorticoid hormones i n the plasma. They include the local metabolism of the glucocorticoid hormo nes into inactive derivatives by the enzyme 11 beta -hydroxysteroid dehydro genase; the intrinsic properties of the MR that discriminate between ligand s through differential contacts; the possibility of forming homo- or hetero dimers between MR and GR, leading to differential transactivation propertie s; and the interactions of MR and GR with other regulatory transcription fa ctors. The relative contribution of each of these successive mechanisms may vary among aldosterone target cells (epithelial vs. nonepithelial) and acc ording to the hormonal context. All these phenomena allow fine tuning of ce llular functions depending on the degree of cooperation between corticoster oid hormones and other factors (hormonal or tissue specific). Such interact ions may be altered in pathophysiological situations.