Membrane glucocorticoid receptor

Membrane glucocorticoid receptors (mGRs) are a group of receptors which bind and are activated by glucocorticoids such as cortisol and corticosterone, as well as certain exogenous glucocorticoids such as dexamethasone.[1][2][3][4][5] Unlike the classical nuclear glucocorticoid receptor (GR), which mediates its effects via genomic mechanisms, mGRs are cell surface receptors which rapidly alter cell signaling via modulation of intracellular signaling cascades.[2][3] The identities of the mGRs have yet to be fully elucidated,[6] but are thought to include membrane-associated classical GRs[7][8] as well as yet-to-be-characterized G protein-coupled receptors (GPCRs).[1][4][9][10] Rapid effects of dexamethasone were found not be reversed by the GR antagonist mifepristone, indicating additional receptors besides just the classical GR.[11]

mGRs have been implicated in the rapid effects of glucocorticoids in the early central stress response[12][13] via modulating neuronal activity in the hypothalamus, hippocampus, amygdala, and prefrontal cortex, among other areas.[7] In accordance, glucocorticoids are known to affect cognition, stress-adaptive behavior, and neuroendocrine output (e.g., suppression of oxytocin and vasopressin secretion)[4] within minutes.[7] mGRs appear to be partially involved in the anti-inflammatory and immunosuppressant effects of glucocorticoids.[3][5][14] mGRs are present in and appear to regulate many major bodily systems and organs, including the cardiovascular, immune, endocrine, and nervous systems, smooth and skeletal muscle, the liver, and fat tissue.[9] mGRs appear to cooperate with, complement, and synergize with classical nuclear GRs in various ways.[15]

See also

References

  1. 1 2 Tasker JG, Di S, Malcher-Lopes R (2006). "Minireview: rapid glucocorticoid signaling via membrane-associated receptors". Endocrinology 147 (12): 5549–56. doi:10.1210/en.2006-0981. PMC 3280589. PMID 16946006.
  2. 1 2 Stahn C, Buttgereit F (2008). "Genomic and nongenomic effects of glucocorticoids". Nat Clin Pract Rheumatol 4 (10): 525–33. doi:10.1038/ncprheum0898. PMID 18762788.
  3. 1 2 3 Grzanka A, Jarzab J (2009). "[Nongenomic effects of glucocorticoids]". Pneumonol Alergol Pol (in Polish) 77 (4): 387–93. PMID 19722144.
  4. 1 2 3 Di S, Tasker JG (2008). "Rapid synapse-specific regulation of hypothalamic magnocellular neurons by glucocorticoids". Prog. Brain Res. 170: 379–88. doi:10.1016/S0079-6123(08)00431-7. PMID 18655897.
  5. 1 2 Löwenberg M, Stahn C, Hommes DW, Buttgereit F (2008). "Novel insights into mechanisms of glucocorticoid action and the development of new glucocorticoid receptor ligands". Steroids 73 (9-10): 1025–9. doi:10.1016/j.steroids.2007.12.002. PMID 18221974.
  6. ↑ Wang C, Liu Y, Cao JM (2014). "G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids". Int J Mol Sci 15 (9): 15412–25. doi:10.3390/ijms150915412. PMC 4200746. PMID 25257522.
  7. 1 2 3 Groeneweg FL, Karst H, de Kloet ER, Joëls M (2011). "Rapid non-genomic effects of corticosteroids and their role in the central stress response". J. Endocrinol. 209 (2): 153–67. doi:10.1530/JOE-10-0472. PMID 21357682.
  8. ↑ Song IH, Buttgereit F (2006). "Non-genomic glucocorticoid effects to provide the basis for new drug developments". Mol. Cell. Endocrinol. 246 (1-2): 142–6. doi:10.1016/j.mce.2005.11.012. PMID 16388891.
  9. 1 2 Kawata M, Hirahara-Wada Y, Matsuda K (2008). "[Membrane-associated steroid hormone receptors: functional significance of nongenomic action]". Nippon Rinsho (in Japanese) 66 (1): 55–62. PMID 18193544.
  10. ↑ Stellato C (2004). "Post-transcriptional and nongenomic effects of glucocorticoids". Proc Am Thorac Soc 1 (3): 255–63. doi:10.1513/pats.200402-015MS. PMID 16113443.
  11. ↑ Urbach V, Verriere V, Grumbach Y, Bousquet J, Harvey BJ (2006). "Rapid anti-secretory effects of glucocorticoids in human airway epithelium". Steroids 71 (4): 323–8. doi:10.1016/j.steroids.2005.09.014. PMID 16298406.
  12. ↑ Sarabdjitsingh RA, Joëls M, de Kloet ER (2012). "Glucocorticoid pulsatility and rapid corticosteroid actions in the central stress response". Physiol. Behav. 106 (1): 73–80. doi:10.1016/j.physbeh.2011.09.017. PMID 21971364.
  13. ↑ Groeneweg FL, Karst H, de Kloet ER, Joëls M (2012). "Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling". Mol. Cell. Endocrinol. 350 (2): 299–309. doi:10.1016/j.mce.2011.06.020. PMID 21736918.
  14. ↑ Löwenberg M, Verhaar AP, van den Brink GR, Hommes DW (2007). "Glucocorticoid signaling: a nongenomic mechanism for T-cell immunosuppression". Trends Mol Med 13 (4): 158–63. doi:10.1016/j.molmed.2007.02.001. PMID 17293163.
  15. ↑ Samarasinghe RA, Witchell SF, DeFranco DB (2012). "Cooperativity and complementarity: synergies in non-classical and classical glucocorticoid signaling". Cell Cycle 11 (15): 2819–27. doi:10.4161/cc.21018. PMC 3419059. PMID 22801547.


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