MineralocorticoidRezeptor

The mineralocorticoid receptor, often abbreviated MR, is a ligand-activated transcription factor in the nuclear receptor superfamily that mediates the actions of mineralocorticoids, especially aldosterone. In humans, MR is encoded by the NR3C2 gene and is expressed in multiple tissues, with high abundance in the kidney distal tubules and collecting ducts, as well as in the colon, heart, and certain brain regions.

Mechanism of action and regulation: In the absence of ligand, MR resides in the cytoplasm bound to heat shock proteins. Upon binding aldosterone, the receptor undergoes conformational changes, translocates to the nucleus, and binds to mineralocorticoid response elements in target gene promoters. This modulates transcription in collaboration with coactivators or corepressors. In the kidney, MR activation increases expression of genes such as SGK1 and certain subunits of the epithelial sodium channel (ENaC), promoting sodium reabsorption and potassium excretion, which influences fluid balance and blood pressure. The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) protects MR from activation by glucocorticoids in mineralocorticoid target tissues by converting cortisol to inactive cortisone. Non-genomic, rapid actions of MR have also been described but are less well characterized.

Physiological and clinical relevance: MR signaling contributes to electrolyte homeostasis, volume status, and blood pressure regulation, and also has roles in the heart and brain related to remodeling, inflammation, and stress responses. Pharmacological MR antagonists, such as spironolactone and eplerenone, block aldosterone-induced MR signaling and are used to treat hypertension, heart failure, and primary hyperaldosteronism. Loss or gain of MR function can lead to salt-wasting disorders or hypertension and edema, respectively.