Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

Glucocorticoid Receptor (GR)

  • Angela Jacques
  • Andrew R. Battle
  • Luke R. Johnson
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101536-1



The gene NR3C1 encoding the glucocorticoid receptor (GR) is located on chromosome 5q31.3 in humans, chromosome 18 in rats and mice, and chromosome 13 in chickens (Flaherty et al. 2012). It counts 2201 bp and contains 15 exons. The five prime untranslated region consists of exon 1 while the protein-encoding region involves exons 2–9. Homologs are conserved in chimpanzees, dogs, rats, zebra fish, and frogs. The structural organization of the GR arises from exons 2 to 9 and includes a DNA-binding domain and hinge region between the N and C termini. Exon 2 codes the N-terminal domain. Exons 3 and 4 encode the DNA-binding domain consisting of two zinc fingers. The GR consists of 777 amino acids and is expressed throughout the body. Subcellular locations include the cytoplasm, mitochondrion, cell nucleus, and plasma membrane. It is...


Chronic Obstructive Pulmonary Disease Glucocorticoid Receptor Fluticasone Propionate Mineralocorticoid Receptor Glucocorticoid Response Element 
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  1. de Kloet ER. From receptor balance to rational glucocorticoid therapy. Endocrinology. 2014;155:2754–69.CrossRefPubMedGoogle Scholar
  2. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. New Engl J Med. 2012;367:107–14. doi:10.1056/NEJMoa1203421.CrossRefPubMedGoogle Scholar
  3. Gametchu B, Watson C, Wu S. Use of receptor antibodies to demonstrate membrane glucocorticoid receptor in cells from human leukemic patients. FASEB J. 1993;7:1283–92.PubMedGoogle Scholar
  4. Haerd T, Gustafsson JA. Structure and function of the DNA-binding domain of the glucocorticoid receptor and other members of the nuclear receptor supergene family. Acc Chem Res. 1993;26:644–50.CrossRefGoogle Scholar
  5. 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. Proc Natl Acad Sci USA. 2016;113:326–31. doi:10.1073/pnas.1518960113.CrossRefPubMedGoogle Scholar
  6. Hudson WH, Youn C, Ortlund EA. The structural basis of direct glucocorticoid-mediated transrepression. Nat Struct Mol Biol. 2013;20:53–U69. doi:10.1038/nsmb.2456.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. 2013;34:518–30.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature. 1991;352:497–505. doi:10.1038/352497a0.CrossRefPubMedGoogle Scholar
  11. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR. DNA binding site sequence directs glucocorticoid receptor structure and activity. Science. 2009;324:407–10. doi:10.1126/science.1164265.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11:141–68.CrossRefPubMedGoogle Scholar
  13. Orchinik M, Murray TF, Moore FL. A corticosteroid receptor in neuronal membranes. Science. 1991;252:1848.CrossRefPubMedGoogle Scholar
  14. Prager EM, Brielmaier J, Bergstrom HC, McGuire J, Johnson LR. Localization of mineralocorticoid receptors at mammalian synapses. PLoS One. 2010;5. doi:10.1371/journal.pone.0014344.Google Scholar
  15. Prager EM, Johnson LR. Stress at the synapse: signal transduction mechanisms of adrenal steroids at neuronal membranes. Sci Signal. 2009;2:re5.CrossRefPubMedGoogle Scholar
  16. Reul J, de Kloet ER. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology. 1985;117:2505–11.CrossRefPubMedGoogle Scholar
  17. 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
  18. Sandi C, Venero C, Guaza C. Novelty-related rapid locomotor effects of corticosterone in rats. Eur J Neurosci. 1996;8:794–800.CrossRefPubMedGoogle Scholar
  19. Tasker JG, Herman JP. Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic–pituitary–adrenal axis. Stress. 2011;14:398–406. doi:10.3109/10253890.2011.586446.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Vilasco M, Communal L, Mourra N, Courtin A, Forgez P, Gompel A. Glucocorticoid receptor and breast cancer. Breast Cancer Res Treat. 2011;130:1–10. doi:10.1007/s10549-011-1689-6.CrossRefPubMedGoogle Scholar
  21. Wolf OT, Atsak P, de Quervain DJ, Roozendaal B, Wingenfeld K. Stress and memory: a selective review on recent developments in the understanding of stress hormone effects on memory and their clinical relevance. J Neuroendocrinol. 2016;28. doi:10.1111/jne.12353.Google Scholar

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© Springer Science+Business Media LLC 2016

Authors and Affiliations

  • Angela Jacques
    • 1
  • Andrew R. Battle
    • 2
  • Luke R. Johnson
    • 1
  1. 1.Queensland University of Technology (QUT)/Institute of Health and Biomedical innovation (IHBI)WoolloongabbaAustralia
  2. 2.School of Biomedical Sciences, Queensland University of Technology (QUT)BrisbaneAustralia