Mineralocorticoid receptor (MR) (MR)

The Mineralocorticoid receptor (MR), encoded by the NR3C2 gene, is a ligand-dependent transcription factor that plays a critical role in regulating electrolyte balance and blood pressure (UniProt P08235). Although its primary physiological ligand is aldosterone, the MR has a high affinity for cortisol; in tissues like the kidney, the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) normally converts cortisol to inactive cortisone to prevent inappropriate MR activation (StatPearls, "Physiology, Aldosterone"). Pathological modulation of the MR pathway via increased cortisol activity occurs when 11β-HSD2 is inhibited or overwhelmed, leading to sodium retention, hypokalemia, and hypertension, a state known as apparent mineralocorticoid excess (PubMed, PMID: 25100070). Therapeutic intervention typically involves Mineralocorticoid Receptor Antagonists (MRAs), such as spironolactone, eplerenone, and the non-steroidal agent finerenone, which are used to treat heart failure and chronic kidney disease by blocking excessive receptor signaling (NIH, "Mineralocorticoid Receptor Antagonists"). These drugs prevent the translocation of the MR to the nucleus, thereby inhibiting the expression of genes that promote inflammation, fibrosis, and salt retention. Furthermore, the development of selective MRAs has aimed to reduce side effects like hyperkalemia and gynecomastia, which are common with older, less selective agents.

Other names

Nuclear receptor subfamily 3 group C member 2Aldosterone receptorNR3C2MR

Competitive antagonism of the mineralocorticoid receptor to inhibit gene transcription associated with sodium retention and fibrosis.