Receptor nomenclature NR3C2
Receptor code 4.10.1:MC:3:C2
Other names MR, MCR, MLR, aldosterone receptor
Molecular information Hs: 984aa, P08235, chr. 4q31.11
Rn: 981aa, P22199, chr. 19q112
Mm: 978aa, Q8VII8, chr. 8 C13
DNA binding
   Structure Homodimer, heterodimer
   HRE core sequence ACAAGANNNTGTTCT (GRE, half-site, palindrome)
Partners HSP90 (physical, functional): cellular localization4; HMGB (physical, functional): DNA binding5,6; 11β-HSD2 (functional): tissue specificity7
Agonists Desoxycorticosterone (1 × 10–11 M), progesterone (1 × 10–11 M),* fludrocortisone (1.2 × 10–10 M), cortisol (1.1–1.5 × 10–10 M), dexamethasone (1 × 10–9 M)* [IC50]8,9; aldosterone (1–1.5 × 10–10)* [Kd]8,9
Antagonists Drospirenone (<1 × 10–10 M), spironolactone (1.4 × 10–8 M), eplerenone (1 × 10–7 M) [IC50]8,1012
Coactivator NCOA1, PGC-1α, ELL1315
Corepressor NCOR1, NCOR2, PIAS116,17
Biologically important isoforms MR-A {Hs, Mm, Rn}: main isoform18; MR-B {Hs, Mm, Rn}: truncated N terminus18; various splice variants also exist resulting in either altered DNA or ligand binding {Hs, Rn}1921
Tissue distribution Liver, brain, heart, kidney, colon, aorta, hippocampus, hypothalamus, adrenal fasciculate, epidermal keratinocytes, neurons of the CNS, cardiac myocytes, endothelial and smooth muscle cells of the vasculature {Hs,Mm,Rn} [Northern blot, Q-PCR, in situ hybridization, Western blot, immunohistology]2233
Functional assay Renal clearance {Mm}34; colonic transepithelial Na+ reabsorption {Mm}34,35
Main target genes Activated: Enac {Hs}36,37 SGK1{Rn},3840 GILZ{Rn}41
Mutant phenotype Homozygous MR-deficient mice have a normal prenatal development; during the 1st week of life, these animals develop symptoms of pseudohypoaldosteronism, lose weight, and eventually die at around day 10 due to kidney failure {Mm} [knockout]34; a conditional knockout model expressing solely in the heart an antisense mRNA directed against the murine MR; within 2–3 months, mice develop severe heart failure in the absence of hypertension or chronic hyperaldosteronism {Mm} [antisense oligonucleotide]3
Human disease Hypertension: Ser810 → Ile SNP causes gain of function42; pseudohypoaldosteronism type 1: various polymorphisms cause loss of activity; autosomal-dominant; haploinsufficiency seems to be the predominant mechanism43,44
  • aa, amino acids; chr., chromosome; HRE, hormone response element; ELL, eleven-nineteen lysine-rich leukemia; HMGB, chromosomal high-mobility group B; 11β-HSD2, 11β-hydroxysteroid dehydrogenase 2; Q-PCR, quantitative polymerase chain reaction; SNP, single-nucleotide polymorphism; GRE, glucocorticoid response element

  • * Radioligand

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