Skip to main content

Glucocorticoid Receptor (GR)

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

Synonyms

GCCR; GCR; GCRST; Glucocorticoid nuclear receptor variant 1; GR; GRL; Nuclear receptor subfamily 3 group C member 1 (glucocorticoid receptor)

Background

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...

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

Access this chapter

Institutional subscriptions

References

  • de Kloet ER. From receptor balance to rational glucocorticoid therapy. Endocrinology. 2014;155:2754–69.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. 2013;34:518–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Orchinik M, Murray TF, Moore FL. A corticosteroid receptor in neuronal membranes. Science. 1991;252:1848.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Prager EM, Johnson LR. Stress at the synapse: signal transduction mechanisms of adrenal steroids at neuronal membranes. Sci Signal. 2009;2:re5.

    Article  PubMed  Google Scholar 

  • Reul J, de Kloet ER. Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology. 1985;117:2505–11.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Sandi C, Venero C, Guaza C. Novelty-related rapid locomotor effects of corticosterone in rats. Eur J Neurosci. 1996;8:794–800.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrew R. Battle .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Jacques, A., Battle, A.R., Johnson, L.R. (2016). Glucocorticoid Receptor (GR). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101536-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101536-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics