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Gene Review

Crhr1  -  corticotropin releasing hormone receptor 1

Mus musculus

Synonyms: CRF 1 receptor, CRF-R-1, CRF-R1, CRF-R1alpha, CRFR-1, ...
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Disease relevance of Crhr1


Psychiatry related information on Crhr1


High impact information on Crhr1

  • We propose that Crhr2 predominantly mediates a central anxiolytic response, opposing the general anxiogenic effect of Crh mediated by Crhr1 [11].
  • Here we report that male, but not female, Crhr2-deficient mice exhibit enhanced anxious behaviour in several tests of anxiety in contrast to mice lacking Crhr1 [11].
  • Here we show that in mice lacking Crhr1, the medulla of the adrenal gland is atrophied and stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone is reduced [12].
  • Crhr1 is highly expressed in the anterior pituitary, neocortex, hippocampus, amygdala and cerebellum, and activation of this receptor stimulates adenylate cyclase [12].
  • In contrast to Crhr1 null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress [13].

Chemical compound and disease context of Crhr1

  • Owing to the important role of 5-HT in the pathophysiology of mood and anxiety disorders, the latter observation may contribute to the therapeutical efficacy of CRH-R1 antagonists in these illnesses [14].

Biological context of Crhr1


Anatomical context of Crhr1


Associations of Crhr1 with chemical compounds

  • Furthermore, testing paired-pulse paradigm revealed a GABA receptor-dependent decrease of paired-pulse ratio in Crhr1(-/-) [21].
  • These results were not due to altered associative learning processes because CRF1+/- and CRF1-/- mice displayed reliable, conditioned place aversions to environmental cues paired with the kappa-opioid receptor agonist U-50,488H [6].
  • Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors [17].
  • These data indicate that resting ACTH secretion in CRF-R1 -/- mice is in part attributable to AVP-dependent mechanisms [22].
  • In the paraventricular nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin expression levels [8].

Physical interactions of Crhr1


Regulatory relationships of Crhr1

  • A 7-day intracerebroventricular infusion of Ucn transiently suppressed ad libitum food intake equally in CRFR1-/- and wild-type mice [1].
  • However, since the effect of 10 nM CRF was additive with that of 1 microM VIP, the CRF receptor was not the site at which high concentrations of VIP stimulated ACTH release [24].
  • However, CRH receptor type 2 mRNA expression is not altered in adult mouse ventricular cardiomyocytes stimulated in vitro with TNFalpha or IL-1alpha [25].
  • Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors [26].

Other interactions of Crhr1


Analytical, diagnostic and therapeutic context of Crhr1


  1. Modulation of urocortin-induced hypophagia and weight loss by corticotropin-releasing factor receptor 1 deficiency in mice. Bradbury, M.J., McBurnie, M.I., Denton, D.A., Lee, K.F., Vale, W.W. Endocrinology (2000) [Pubmed]
  2. 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]
  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. Corticotropin-releasing factor receptor 1-deficient mice do not develop postoperative gastric ileus. Luckey, A., Wang, L., Jamieson, P.M., Basa, N.R., Million, M., Czimmer, J., Vale, W., Taché, Y. Gastroenterology (2003) [Pubmed]
  5. Corticotropin-releasing factor stimulates phospholipid methylation and corticotropin secretion in mouse pituitary tumor cells. Hook, V.Y., Heisler, S., Axelrod, J. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  6. The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. Contarino, A., Papaleo, F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1. Contarino, A., Dellu, F., Koob, G.F., Smith, G.W., Lee, K.F., Vale, W., Gold, L.H. Brain Res. (1999) [Pubmed]
  8. Differential disinhibition of the neonatal hypothalamic- pituitary-adrenal axis in brain-specific CRH receptor 1-knockout mice. Schmidt, M.V., Deussing, J.M., Oitzl, M.S., Ohl, F., Levine, S., Wurst, W., Holsboer, F., M??ller, M.B., de Kloet, E.R. Eur. J. Neurosci. (2006) [Pubmed]
  9. Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919). Post, A., Ohl, F., Almeida, O.F., Binder, E.B., Rücker, M., Welt, S., Binder, E., Holsboer, F., Sillaber, I. Psychopharmacology (Berl.) (2005) [Pubmed]
  10. Disruption of feeding behavior in CRH receptor 1-deficient mice is dependent on glucocorticoids. Müller, M.B., Keck, M.E., Zimmermann, S., Holsboer, F., Wurst, W. Neuroreport (2000) [Pubmed]
  11. 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]
  12. Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Timpl, P., Spanagel, R., Sillaber, I., Kresse, A., Reul, J.M., Stalla, G.K., Blanquet, V., Steckler, T., Holsboer, F., Wurst, W. Nat. Genet. (1998) [Pubmed]
  13. Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress. Müller, M.B., Zimmermann, S., Sillaber, I., Hagemeyer, T.P., Deussing, J.M., Timpl, P., Kormann, M.S., Droste, S.K., Kühn, R., Reul, J.M., Holsboer, F., Wurst, W. Nat. Neurosci. (2003) [Pubmed]
  14. Altered serotonergic neurotransmission but normal hypothalamic-pituitary-adrenocortical axis activity in mice chronically treated with the corticotropin-releasing hormone receptor type 1 antagonist NBI 30775. Oshima, A., Flachskamm, C., Reul, J.M., Holsboer, F., Linthorst, A.C. Neuropsychopharmacology (2003) [Pubmed]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. Mouse corticotropin-releasing factor receptor type 2alpha gene: isolation, distribution, pharmacological characterization and regulation by stress and glucocorticoids. Chen, A., Perrin, M., Brar, B., Li, C., Jamieson, P., Digruccio, M., Lewis, K., Vale, W. Mol. Endocrinol. (2005) [Pubmed]
  20. Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: localization, basal expression in corticotropin-releasing factor receptor (CRFR) 1- and CRFR2-null mice, and regulation by glucocorticoids. Chen, A., Blount, A., Vaughan, J., Brar, B., Vale, W. Endocrinology (2004) [Pubmed]
  21. Corticotropin-releasing factor (CRF) receptor type 1-dependent modulation of synaptic plasticity. Schierloh, A., Deussing, J., Wurst, W., Zieglgänsberger, W., Rammes, G. Neurosci. Lett. (2007) [Pubmed]
  22. CRF type I receptor-deficient mice exhibit a pronounced pituitary-adrenal response to local inflammation. Turnbull, A.V., Smith, G.W., Lee, S., Vale, W.W., Lee, K.F., Rivier, C. Endocrinology (1999) [Pubmed]
  23. Localization of the type 1 corticotropin releasing factor receptor (CRF-R1) in the embryonic mouse cerebellum. King, J.S., Bishop, G.A. J. Neurocytol. (2003) [Pubmed]
  24. Peptide specificity for stimulation of corticotropin secretion: activation of overlapping pathways by the vasoactive intestinal peptide family and corticotropin-releasing factor. Westendorf, J.M., Schonbrunn, A. Endocrinology (1985) [Pubmed]
  25. 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]
  26. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. Winsky-Sommerer, R., Yamanaka, A., Diano, S., Borok, E., Roberts, A.J., Sakurai, T., Kilduff, T.S., Horvath, T.L., de Lecea, L. J. Neurosci. (2004) [Pubmed]
  27. Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotropin-releasing hormone receptor 1 is dependent on glucocorticoids. Müller, M.B., Landgraf, R., Preil, J., Sillaber, I., Kresse, A.E., Keck, M.E., Zimmermann, S., Holsboer, F., Wurst, W. Endocrinology (2000) [Pubmed]
  28. Detection of corticotropin-releasing hormone receptor 1 immunoreactivity in cholinergic, dopaminergic and noradrenergic neurons of the murine basal forebrain and brainstem nuclei--potential implication for arousal and attention. Sauvage, M., Steckler, T. Neuroscience (2001) [Pubmed]
  29. Corticotropin-releasing factor (CRF) agonists stimulate testosterone production in mouse leydig cells through CRF receptor-1. Heinrich, N., Meyer, M.R., Furkert, J., Sasse, A., Beyermann, M., Bönigk, W., Berger, H. Endocrinology (1998) [Pubmed]
  30. Modulation of learning and anxiety by corticotropin-releasing factor (CRF) and stress: differential roles of CRF receptors 1 and 2. Radulovic, J., Rühmann, A., Liepold, T., Spiess, J. J. Neurosci. (1999) [Pubmed]
  31. Dissociation of locomotor activation and suppression of food intake induced by CRF in CRFR1-deficient mice. Contarino, A., Dellu, F., Koob, G.F., Smith, G.W., Lee, K.F., Vale, W.W., Gold, L.H. Endocrinology (2000) [Pubmed]
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