Mineralocorticoid Receptor - Function

Function

MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports (mainly the epithelial sodium channel or ENaC, Na+/K+ pump, serum and glucocorticoid induced kinase or SGK1) resulting in the reabsoprtion of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure, and an excretion of potassium to maintain a normal salt concentration in the body.

The receptor is activated by mineralocorticoids such as aldosterone and deoxycorticosterone as well as glucocorticoids, like cortisol. In intact animals, the mineralocorticoid receptor is "protected" from glucocorticoids by co-localization of an enzyme, Corticosteroid 11-beta-dehydrogenase isozyme 2 (11ß-HSD2), that converts cortisol to inactive cortisone. It also responds to some progestins. Spironolactone and eplerenone are mineralocorticoid receptor antagonists.

Activation of the mineralocorticoid receptor, upon the binding of its ligand aldosterone, results in its translocation to the cell nucleus, homodimerization and binding to hormone response elements present in the promoter of some genes. This results in the complex recruitment of the transcriptional machinery and the transcription into mRNA of the DNA sequence of the activated genes.