Themineralocorticoid receptor (orMR,MLR,MCR), also known as thealdosterone receptor ornuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by theNR3C2gene that is located on chromosome 4q31.1-31.2.[5]
MR is a receptor with equalaffinity formineralocorticoids and glucocorticoids. It belongs to thenuclear receptor family where theligand diffuses into cells, interacts with the receptor and results in asignal transduction affecting specific gene expression in thenucleus. The selective response of some tissues and organs to mineralocorticoids over glucocorticoids occurs because mineralocorticoid-responsive cells expressCorticosteroid 11-beta-dehydrogenase isozyme 2, an enzyme which selectively inactivates glucocorticoids more readily than mineralocorticoids.
The receptor is activated by mineralocorticoids such asaldosterone and its precursordeoxycorticosterone as well asglucocorticoids likecortisol. In intact animals, the mineralocorticoid receptor is "protected" from glucocorticoids by co-localization of an enzyme,corticosteroid 11-beta-dehydrogenase isozyme 2 (a.k.a. 11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone.[6]
Activation of the mineralocorticoid receptor, upon the binding of its ligand aldosterone, results in itstranslocation to the cell nucleus,homodimerization and binding tohormone response elements present in thepromoter of some genes. This results in the complex recruitment of the transcriptional machinery and thetranscription intomRNA of theDNA sequence of the activated genes.[7]
An activating mutation in the NR3C2 gene (S810L) results in constitutive activity of the mineralocorticoid receptor, leading to severe early-onsethypertension that is exacerbated by pregnancy. In a family known to harbor the S810L mutation, 3 individuals carrying the mutation died ofchronic heart failure before age 50.[8] Additional studies have shown that this activated version of MR can positively respond to ligands that are traditionallyantagonists, such as endogenous hormones likeprogesterone, and the diuretic drugsspironolactone andeplerenone.[8]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB (1989). "The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2".Cytogenetics and Cell Genetics.52 (1–2):83–4.doi:10.1159/000132846.PMID2558856.
^Edwards CR, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, et al. (October 1988). "Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor".Lancet.2 (8618):986–9.doi:10.1016/S0140-6736(88)90742-8.hdl:1874/24458.PMID2902493.S2CID206004965.
Sheppard KE (May 2002). "Nuclear receptors. II. Intestinal corticosteroid receptors".American Journal of Physiology. Gastrointestinal and Liver Physiology.282 (5): G742-6.doi:10.1152/ajpgi.00531.2001.PMID11960770.
Kjellander CG (March 1975). "[The psychotherapeutic society--utopia or nightmare?]".Läkartidningen.72 (12):1160–1.PMID1134129.
Morrison N, Harrap SB, Arriza JL, Boyd E, Connor JM (June 1990). "Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1".Human Genetics.85 (1):130–2.doi:10.1007/BF00276340.PMID2162806.S2CID9264993.
Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB (1989). "The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2".Cytogenetics and Cell Genetics.52 (1–2):83–4.doi:10.1159/000132846.PMID2558856.
Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM (July 1987). "Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor".Science.237 (4812):268–75.Bibcode:1987Sci...237..268A.doi:10.1126/science.3037703.PMID3037703.
Bloem LJ, Guo C, Pratt JH (November 1995). "Identification of a splice variant of the rat and human mineralocorticoid receptor genes".The Journal of Steroid Biochemistry and Molecular Biology.55 (2):159–62.doi:10.1016/0960-0760(95)00162-S.PMID7495694.S2CID10179119.
Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G (1997). "The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52".Receptors & Signal Transduction.7 (2):85–98.PMID9392437.
Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP (July 1998). "Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I".Nature Genetics.19 (3):279–81.doi:10.1038/966.PMID9662404.S2CID33028408.
Lupo B, Mesnier D, Auzou G (September 1998). "Cysteines 849 and 942 of human mineralocorticoid receptor are crucial for steroid binding".Biochemistry.37 (35):12153–9.doi:10.1021/bi980593e.PMID9724527.
Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, et al. (July 1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis".Nature Genetics.22 (3):239–47.doi:10.1038/10297.PMID10391210.S2CID4636523.
Watzka M, Beyenburg S, Blümcke I, Elger CE, Bidlingmaier F, Stoffel-Wagner B (August 2000). "Expression of mineralocorticoid and glucocorticoid receptor mRNA in the human hippocampus".Neuroscience Letters.290 (2):121–4.doi:10.1016/S0304-3940(00)01325-2.PMID10936692.S2CID45158226.
1gdc: REFINED SOLUTION STRUCTURE OF THE GLUCOCORTICOID RECEPTOR DNA-BINDING DOMAIN
1rgd: STRUCTURE REFINEMENT OF THE GLUCOCORTICOID RECEPTOR-DNA BINDING DOMAIN FROM NMR DATA BY RELAXATION MATRIX CALCULATIONS
1y9r: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to deoxycorticosterone and harboring the S810L mutation responsible for a severe form of hypertension
1ya3: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to progesterone and harboring the S810L mutation responsible for a severe form of hypertension
2a3i: Structural and Biochemical Mechanisms for the Specificity of Hormone Binding and Coactivator Assembly by Mineralocorticoid Receptor
2aa2: Mineralocorticoid Receptor with Bound Aldosterone
2aa5: Mineralocorticoid Receptor with Bound Progesterone
2aa6: Mineralocorticoid Receptor S810L Mutant with Bound Progesterone
2aa7: Mineralocorticoid Receptor with Bound Deoxycorticosterone
2aax: Mineralocorticoid Receptor Double Mutant with Bound Cortisone
2ab2: Mineralocorticoid Receptor Double Mutant with Bound Spironolactone
2abi: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to deoxycorticosterone
2gda: REFINED SOLUTION STRUCTURE OF THE GLUCOCORTICOID RECEPTOR DNA-BINDING DOMAIN
