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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. ^ a b 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. ^ a b 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. S2CID  22686260.
  3. ^ a b c Grzanka A, Jarzab J (2009). "[Nongenomic effects of glucocorticoids]". Pneumonol Alergol Pol (in Polish). 77 (4): 387–93. PMID  19722144.
  4. ^ a b c Di S, Tasker JG (2008). "Rapid synapse-specific regulation of hypothalamic magnocellular neurons by glucocorticoids". Advances in Vasopressin and Oxytocin — from Genes to Behaviour to Disease. Progress in Brain Research. Vol. 170. pp. 379–88. doi: 10.1016/S0079-6123(08)00431-7. ISBN  9780444532015. PMID  18655897. {{ cite book}}: |journal= ignored ( help)
  5. ^ a b 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. S2CID  25043357.
  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. ^ a b c 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. S2CID  40239838.
  9. ^ a b 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. S2CID  22478627.
  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. S2CID  32448734.
  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. S2CID  23048944.
  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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