Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Mineralocorticoid Receptor

  • Angela Jacques
  • Luke R. JohnsonEmail author
  • Andrew R. Battle
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101537


Historical Background

Located on chromosome 4q31.1 in humans, the gene NR3C2 encodes the mineralocorticoid receptor (Fan et al. 1989; Morrison et al. 1990). It has 5201 bp, an exon count of 12, and is located on chromosome 8 in mice, 19 in rats, 1 in zebra fish, and 4 in chickens. Mineralocorticoids (MRs) belong to the nuclear receptor subfamily 3 and are distributed throughout the epithelia of the kidneys, sweat glands, and colon and the nonepithelial tissues of the heart and brain. The human MR was first cloned in 1987, consists of 984 amino acids, and is similar in structure to the glucocorticoid receptor, sharing 94% identity in the DNA-binding domain (Funder 1997).

It is unique among steroid receptors in that it plays signaling roles in both mineralocorticoids (e.g., aldosterone and deoxycorticosterone) and the glucocorticoids (cortisol in humans, corticosterone in rats). In particular,...

This is a preview of subscription content, log in to check access.


  1. Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, et al. The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52. Recept Sig Transduct. 1996;7:85–98.Google Scholar
  2. de Kloet ER. From receptor balance to rational glucocorticoid therapy. Endocrinology. 2014;155:2754–69.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Shows TB. Assignment of human mineralocorticoid receptor (Mlr) to human chromosome-4q31.2. Cytogenet Cell Genet. 1989;51:996.Google Scholar
  4. Funder JW. Glucocorticoid and mineralocorticoid receptors: biology and clinical relevance. Annu Rev Med. 1997;48:231–40. doi:10.1146/annurev.med.48.1.231.CrossRefPubMedGoogle Scholar
  5. Gomez-Sanchez E, Gomez-Sanchez CE. The multifaceted mineralocorticoid receptor. Compr Physiol. 2014;4:965–94. doi:10.1002/cphy.c130044.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Hudson WH, Kossmann BR, de Vera IMS, Chuo SW, Weikum ER, Eick GN, et al. Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space. P Natl Acad Sci USA. 2016;113:326–31. doi:10.1073/pnas.1518960113.CrossRefGoogle Scholar
  7. Hudson WH, Youn C, Ortlund EA. Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA. PLoS One. 2014;9. doi:ARTN e10700081371/journal.pone.0107000.Google Scholar
  8. Joels M. Stress hormone actions in brain, in health disease – possibilities for new pharmacotherapies – preface. Eur J Pharmacol. 2008;583:173. doi:10.1016/j.ejphar.2008.01.002.CrossRefPubMedGoogle Scholar
  9. Joels M, Sarabdjitsingh RA, Karst H. Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes. Pharmacol Rev. 2012;64:901–38. doi:10.1124/pr.112.005892.CrossRefPubMedCentralPubMedGoogle Scholar
  10. Johnson LR, Farb C, Morrison J, McEwen B, LeDoux J. Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala. Neuroscience. 2005;136:289–99.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Karst H, Berger S, Turiault M, Tronche F, Schutz G, Joels M. Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. P Natl Acad Sci USA. 2005;102:19204–7. doi:10.1073/pnas.0507572102.CrossRefGoogle Scholar
  12. Krozowski ZS, Funder JW. Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity. P Natl Acad Sci-Biol. 1983;80:6056–60. doi:10.1073/pnas.80.19.6056.CrossRefGoogle Scholar
  13. Morrison N, Harrap SB, Arriza JL, Boyd E, Connor JM. Regional chromosomal assignment of the human mineralocorticoid receptor gene to 4q31.1. Hum Genet. 1990;85:130–2.CrossRefPubMedGoogle Scholar
  14. Pawlak M, Lefebvre P, Staels B. General molecular biology and architecture of nuclear receptors. Curr Top Med Chem. 2012;12:486–504.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Prager EM, Brielmaier J, Bergstrom HC, McGuire J, Johnson LR. Localization of mineralocorticoid receptors at mammalian synapses. PLoS One. 2010;5. doi:ARTN e14344171371/journal.pone.0014344.Google Scholar
  16. Prager EM, Johnson LR. Stress at the synapse: signal transduction mechanisms of adrenal steroids at neuronal membranes. Sci Signal. 2009;2:re5-re.CrossRefGoogle Scholar
  17. Reul J, Kloet E. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology. 1985;117:2505–11.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Rogerson FM, Dimopoulos N, Sluka P, Chu S, Curtis AJ, Fuller PJ. Structural determinants of aldosterone binding selectivity in the mineralocorticoid receptor. J Biol Chem. 1999;274:36305–11. doi:10.1074/jbc.274.51.36305.CrossRefPubMedGoogle Scholar
  19. Rupprecht R, Reul JM, van Steensel B, Spengler D, Söder M, Berning B, et al. Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol Mol Pharmacol. 1993;247:145–54.CrossRefGoogle Scholar
  20. Russo MF, Loy SRA, Battle AR, Johnson LR. Membrane associated synaptic mineralocorticoid and glucocorticoid receptors are rapid regulators of dendritic spines. Front Cell Neurosci. 2016;10.Google Scholar
  21. Sarabdjitsingh RA, Joels M. Rapid corticosteroid actions on synaptic plasticity in the mouse basolateral amygdala: relevance of recent stress history and beta-adrenergic signaling. Neurobiol Learn Mem. 2014;112:168–75. doi:10.1016/j.nlm.2013.10.011.CrossRefPubMedGoogle Scholar
  22. Sturm A, Bury N, Dengreville L, Fagart J, Flouriot G, Rafestin-Oblin ME, et al. 11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor. Endocrinology. 2005;146:47–55. doi:10.1210/en.2004-0128.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Angela Jacques
    • 1
    • 2
  • Luke R. Johnson
    • 1
    • 2
    Email author
  • Andrew R. Battle
    • 3
    • 4
  1. 1.Queensland University of Technology (QUT)/Institute of Health and Biomedical Innovation (IHBI)WoolloongabbaAustralia
  2. 2.Translational Research Institute/IHBI/QUTBrisbaneAustralia
  3. 3.School of Biomedical Sciences, Queensland University of Technology (QUT)BrisbaneAustralia
  4. 4.Translational Research Institute/IHBI/School of Biomedical Science QUTBrisbaneAustralia