Mineralocorticoid receptor (NR3C2) (MR)

The mineralocorticoid receptor (MR), encoded by the NR3C2 gene, is a ligand-dependent transcription factor and member of the nuclear receptor superfamily (UniProt P08235). It is primarily expressed in the distal nephron of the kidney, where it regulates sodium reabsorption and potassium excretion to maintain fluid and electrolyte homeostasis (StatPearls, Mineralocorticoid Antagonists). Beyond the kidney, MR is expressed in the heart, vasculature, and central nervous system, where its overactivation contributes to inflammation, oxidative stress, and progressive fibrosis (NCBI, Gene ID: 677). Pathological MR signaling is a key driver in the progression of chronic kidney disease (CKD) and heart failure with reduced ejection fraction (HFrEF) (PubMed, PMID: 32835708). Therapeutic intervention typically involves mineralocorticoid receptor antagonists (MRAs), which are classified into steroidal agents like spironolactone and eplerenone, and newer non-steroidal agents like finerenone (FDA, Kerendia Label). These drugs are essential for reducing cardiovascular mortality and slowing renal decline, though they carry a significant risk of hyperkalemia, necessitating regular monitoring of serum potassium levels (AHA/ACC Guidelines).

Other names

Nuclear receptor subfamily 3 group C member 2NR3C2Aldosterone receptorMCRMLR

Mineralocorticoid receptor antagonists (MRAs) bind to the ligand-binding domain of the MR, preventing the binding of endogenous agonists like aldosterone and cortisol. This inhibition prevents the receptor from translocating to the nucleus and binding to hormone response elements, thereby blocking the expression of genes such as SCNN1A (ENaC) and ATP1A1 (Na+/K+-ATPase) that promote sodium retention and potassium loss (StatPearls, Mineralocorticoid Receptor Antagonists).