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Gene Review

Crhr2  -  corticotropin releasing hormone receptor 2

Mus musculus

Synonyms: CRF 2 receptor, CRF-R-2, CRF-R2, CRF-RB, CRFR-2, ...
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Disease relevance of Crhr2

  • Both respond with increased edema formation in response to thermal exposure, however, indicating that in contrast to its central role in anxiety, the peripheral role of Crhr2 in vascular permeability is independent of gender [1].
  • We propose the use of CRFR2 selective agonists, Ucn-II and Ucn-III, to treat ischemic heart disease because of their potent cardioprotective effects in the murine heart and their minimal impact on the hypothalamic stress axis [2].
  • Use of the G(i) and G(o) protein inhibitor pertussis toxin showed that ERK1/2-p42, 44 activation by Ucn-I via CRFR1 and CRFR2beta are both G(i) and/or G(o) protein dependent [3].
  • Similarly, the tachycardia was effectively blocked by preinjection of the CRFR2 antagonist antisauvagine-30 [4].
  • Ethanol-induced conditioned taste aversion (CTA), loss of righting reflex (LORR), hypothermia, and ethanol metabolism kinetics were also examined in the CRF2 KO and WT mice [5].

Psychiatry related information on Crhr2


High impact information on Crhr2

  • Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues [7].
  • We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn [8].
  • Although initiation of the stress response appears to be normal, Crhr2-/- mice show early termination of adrenocorticotropic hormone (Acth) release, suggesting that Crhr2 is involved in maintaining HPA drive [8].
  • Moreover, Crhr2-/- mice have elevated basal blood pressure, demonstrating that Crhr2 participates in cardiovascular homeostasis [8].
  • In addition to central nervous system effects, we found that, in contrast to wild-type mice, Crhr2-/- mice fail to show the enhanced cardiac performance or reduced blood pressure associated with systemic Ucn, suggesting that Crhr2 mediates these peripheral haemodynamic effects [8].

Biological context of Crhr2


Anatomical context of Crhr2


Associations of Crhr2 with chemical compounds


Regulatory relationships of Crhr2


Other interactions of Crhr2


Analytical, diagnostic and therapeutic context of Crhr2

  • By using RT-PCR and Southern hybridization, the relative mRNA expression levels of full-length (seven transmembrane domains) CRFR2alpha and the soluble form (sCRFR2alpha) in the mouse brain were measured with a single reaction [25].
  • Urocortin (Ucn)-I activation of CRFR2beta is cardioprotective against ischemic reperfusion (I/R) injury by stimulation of the ERKs1/2 p42, 44 [2].
  • By single cell PCR, the authors show that microglia and astrocytes express mRNA for both CRH-R1 and CRH-R2 [26].
  • Further, by means of RT-PCR and in situ hybridization analyses, we could provide first evidence that both CRHR1 and CRHR2 are expressed in the mouse pituitary and adrenal cortex [27].
  • In the present study, the postnatal (P) development (P0-P14) and cellular localization of CRF-R2 in different cell types was analyzed using PAP and double-label fluorescent immunohistochemistry; cell-specific antibodies were used to identify cells expressing CRF-R2 at different stages of postnatal development [24].


  1. Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Kishimoto, T., Radulovic, J., Radulovic, M., Lin, C.R., Schrick, C., Hooshmand, F., Hermanson, O., Rosenfeld, M.G., Spiess, J. Nat. Genet. (2000) [Pubmed]
  2. Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart. Brar, B.K., Jonassen, A.K., Egorina, E.M., Chen, A., Negro, A., Perrin, M.H., Mjøs, O.D., Latchman, D.S., Lee, K.F., Vale, W. Endocrinology (2004) [Pubmed]
  3. Specificity and regulation of extracellularly regulated kinase1/2 phosphorylation through corticotropin-releasing factor (CRF) receptors 1 and 2beta by the CRF/urocortin family of peptides. Brar, B.K., Chen, A., Perrin, M.H., Vale, W. Endocrinology (2004) [Pubmed]
  4. Stress-mediated heart rate dynamics after deletion of the gene encoding corticotropin-releasing factor receptor 2. Stiedl, O., Meyer, M., Kishimoto, T., Rosenfeld, M.G., Spiess, J. Eur. J. Neurosci. (2003) [Pubmed]
  5. Mice deficient in corticotropin-releasing factor receptor type 2 exhibit normal ethanol-associated behaviors. Sharpe, A.L., Coste, S.C., Burkhart-Kasch, S., Li, N., Stenzel-Poore, M.P., Phillips, T.J. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  6. Corticotropin-releasing factor receptors CRF1 and CRF2 exert both additive and opposing influences on defensive startle behavior. Risbrough, V.B., Hauger, R.L., Roberts, A.L., Vale, W.W., Geyer, M.A. J. Neurosci. (2004) [Pubmed]
  7. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Bale, T.L., Contarino, A., Smith, G.W., Chan, R., Gold, L.H., Sawchenko, P.E., Koob, G.F., Vale, W.W., Lee, K.F. Nat. Genet. (2000) [Pubmed]
  8. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Coste, S.C., Kesterson, R.A., Heldwein, K.A., Stevens, S.L., Heard, A.D., Hollis, J.H., Murray, S.E., Hill, J.K., Pantely, G.A., Hohimer, A.R., Hatton, D.C., Phillips, T.J., Finn, D.A., Low, M.J., Rittenberg, M.B., Stenzel, P., Stenzel-Poore, M.P. Nat. Genet. (2000) [Pubmed]
  9. Distribution and expression of CRF receptor 1 and 2 mRNAs in the CRF over-expressing mouse brain. Korosi, A., Veening, J.G., Kozicz, T., Henckens, M., Dederen, J., Groenink, L., van der Gugten, J., Olivier, B., Roubos, E.W. Brain Res. (2006) [Pubmed]
  10. Corticotropin-releasing factor and the urocortins induce the expression of TLR4 in macrophages via activation of the transcription factors PU.1 and AP-1. Tsatsanis, C., Androulidaki, A., Alissafi, T., Charalampopoulos, I., Dermitzaki, E., Roger, T., Gravanis, A., Margioris, A.N. J. Immunol. (2006) [Pubmed]
  11. Mapping of the mouse corticotropin-releasing hormone receptor 2 gene (Crhr2) to chromosome 6. Lesh, J.S., Burrows, H.L., Seasholtz, A.F., Camper, S.A. Mamm. Genome (1997) [Pubmed]
  12. Vital functions of corticotropin-releasing factor (CRF) pathways in maintenance and regulation of energy homeostasis. Carlin, K.M., Vale, W.W., Bale, T.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. Activation of the CRF 2 receptor modulates skeletal muscle mass under physiological and pathological conditions. Hinkle, R.T., Donnelly, E., Cody, D.B., Samuelsson, S., Lange, J.S., Bauer, M.B., Tarnopolsky, M., Sheldon, R.J., Coste, S.C., Tobar, E., Stenzel-Poore, M.P., Isfort, R.J. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  14. Corticotropin-releasing hormone activates ERK1/2 MAPK in specific brain areas. Refojo, D., Echenique, C., Müller, M.B., Reul, J.M., Deussing, J.M., Wurst, W., Sillaber, I., Paez-Pereda, M., Holsboer, F., Arzt, E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Corticotropin-releasing factor receptor 2 is a tonic suppressor of vascularization. Bale, T.L., Giordano, F.J., Hickey, R.P., Huang, Y., Nath, A.K., Peterson, K.L., Vale, W.W., Lee, K.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Nie, Z., Schweitzer, P., Roberts, A.J., Madamba, S.G., Moore, S.D., Siggins, G.R. Science (2004) [Pubmed]
  17. Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. Ungless, M.A., Singh, V., Crowder, T.L., Yaka, R., Ron, D., Bonci, A. Neuron (2003) [Pubmed]
  18. Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. Chen, A., Brar, B., Choi, C.S., Rousso, D., Vaughan, J., Kuperman, Y., Kim, S.N., Donaldson, C., Smith, S.M., Jamieson, P., Li, C., Nagy, T.R., Shulman, G.I., Lee, K.F., Vale, W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  19. Modulation of corticotropin-releasing hormone receptor type 2 mRNA expression by CRH deficiency or stress in the mouse heart. Pournajafi Nazarloo, H., Tanaka, Y., Dorobantu, M., Hashimoto, K. Regul. Pept. (2003) [Pubmed]
  20. Urocortin 1 and Urocortin 2 induce macrophage apoptosis via CRFR2. Tsatsanis, C., Androulidaki, A., Dermitzaki, E., Charalampopoulos, I., Spiess, J., Gravanis, A., Margioris, A.N. FEBS Lett. (2005) [Pubmed]
  21. IL-1alpha and TNFalpha down-regulate CRH receptor-2 mRNA expression in the mouse heart. Coste, S.C., Heldwein, K.A., Stevens, S.L., Tobar-Dupres, E., Stenzel-Poore, M.P. Endocrinology (2001) [Pubmed]
  22. Perfluorooctane sulfonate influences feeding behavior and gut motility via the hypothalamus. Asakawa, A., Toyoshima, M., Fujimiya, M., Harada, K., Ataka, K., Inoue, K., Koizumi, A. Int. J. Mol. Med. (2007) [Pubmed]
  23. The cardiovascular physiologic actions of urocortin II: acute effects in murine heart failure. Bale, T.L., Hoshijima, M., Gu, Y., Dalton, N., Anderson, K.R., Lee, K.F., Rivier, J., Chien, K.R., Vale, W.W., Peterson, K.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  24. Evidence for an axonal localization of the type 2 corticotropin-releasing factor receptor during postnatal development of the mouse cerebellum. Lee, K.H., Bishop, G.A., Tian, J.B., King, J.S. Exp. Neurol. (2004) [Pubmed]
  25. A soluble mouse brain splice variant of type 2alpha corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity. Chen, A.M., Perrin, M.H., Digruccio, M.R., Vaughan, J.M., Brar, B.K., Arias, C.M., Lewis, K.A., Rivier, J.E., Sawchenko, P.E., Vale, W.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  26. Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: a potential link to microglia and atrocytes that express CRH-R1. Stevens, S.L., Shaw, T.E., Dykhuizen, E., Lessov, N.S., Hill, J.K., Wurst, W., Stenzel-Poore, M.P. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  27. Expression of CRHR1 and CRHR2 in mouse pituitary and adrenal gland: implications for HPA system regulation. Müller, M.B., Preil, J., Renner, U., Zimmermann, S., Kresse, A.E., Stalla, G.K., Keck, M.E., Holsboer, F., Wurst, W. Endocrinology (2001) [Pubmed]
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