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Gene Review

Crhr1  -  corticotropin releasing hormone receptor 1

Rattus norvegicus

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

  • The rCRF-R is 97% identical at the amino acid level to the human pituitary tumor CRF receptor, differing by only 12 amino acids [1].
  • Having recently characterized the human pituitary CRF receptor by expression cloning of cDNA from a human Cushing's corticotropic adenoma, we report here the structure of the cDNA for a rat brain CRF receptor (rCRF-R) which was cloned by hybridization from a rat brain cDNA library [1].
  • Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis [2].
  • These studies demonstrated changes in the expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats [3].
  • These data suggest that decreased food intake and weight loss after high-dose Cort administration at least partially depend on the profound impact of Cort on plasma leptin secretion in the rat; they suggest, moreover, an additional mechanism for the satiety-inducing effects of leptin, namely increasing CRHR-2 in the VMH [4].

Psychiatry related information on Crhr1


High impact information on Crhr1

  • We found that antalarmin, a CRH receptor type 1 antagonist, decreased FasL expression and promoted apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and inhibited by antalarmin [8].
  • Leptin affects food intake via CRF-receptor-mediated pathways [9].
  • First, LTD induction was effectively blocked by specific CRF receptor antagonists, alpha-helical CRF-(9-41) (alpha-h CRF) and astressin; and second, LTD was no longer observed in CF-deprived cerebella but was restored by CRF replenishment [10].
  • The pattern of CRF receptor mRNA expression in the brain, pituitary gland, and other organs corresponds precisely to that predicted for the classic CRF receptor, suggesting that this receptor serves to mediate the known biological effects of CRF on behavior, stress, and homeostasis [11].
  • In the brain, CRF 2 receptor, but not CRF 1 receptor, is involved in this action [12].

Chemical compound and disease context of Crhr1


Biological context of Crhr1

  • Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locus ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN [18].
  • The temporal and anatomic selectivity of the ovarian periovulatory CRF1 receptor gene expression may suggest a critical biological action of CRF during the ovulatory process and suggests that the intraovarian environment may influence the stress-induced transcription of a selective CRF receptor subtype within the ovary [19].
  • Interestingly, immobilization stress induced a marked expression of CRF1 receptor mRNA in the stroma cells in the afternoon of proestrus, suggesting that the ovaries may be sensitive to acute neurogenic challenge during the preovulatory stage [19].
  • These results provide clear evidence that the gene encoding the CRF1 receptor but not the type 2 receptors can be finely induced in selective ovarian compartments in both control and stressful conditions during the gonadal life cycle [19].
  • Urocortin (Ucn) is a closely related mammalian peptide that binds to both identified CRH receptor subtypes and also reduces food intake when administered i3vt [20].

Anatomical context of Crhr1


Associations of Crhr1 with chemical compounds


Physical interactions of Crhr1

  • The actions of CRF are mediated by G-protein coupled membrane bound receptors and a high affinity CRF receptor, CRF1, has been previously cloned and functionally characterized [21].

Regulatory relationships of Crhr1


Other interactions of Crhr1

  • This heterogeneous distribution of CRF1 and CRF2 receptor mRNA suggests distinctive functional roles for each receptor in CRF-related systems [21].
  • Employing a double-immunocytochemical technique, this study investigated in Wistar rats with Freund's complete adjuvant-induced hind paw inflammation whether immune cells within blood and inflamed subcutaneous tissue express CRH R1 and/or CRH R2 together with the opioid peptide beta-endorphin (END) [27].
  • GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1-antagonist treated nonhandled rats to levels commensurate with those in handled cohorts [28].
  • These results suggest that the cardiac effects of Ucn may be mediated by a CRF receptor, and prostaglandins may be involved in the vasodilator effect [29].
  • Distribution of corticotropin releasing hormone receptor immunoreactivity in the rat hypothalamus: coexpression in neuropeptide Y and dopamine neurons in the arcuate nucleus [30].

Analytical, diagnostic and therapeutic context of Crhr1


  1. Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor. Perrin, M.H., Donaldson, C.J., Chen, R., Lewis, K.A., Vale, W.W. Endocrinology (1993) [Pubmed]
  2. Neuronal activity and CRF receptor gene transcription in the brains of rats with colitis. Porcher, C., Sinniger, V., Juhem, A., Mouchet, P., Bonaz, B. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  3. Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis. LaBerge, J., Malley, S.E., Zvarova, K., Vizzard, M.A. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  4. Altered expression of type 2 CRH receptor mRNA in the VMH by glucocorticoids and starvation. Makino, S., Nishiyama, M., Asaba, K., Gold, P.W., Hashimoto, K. Am. J. Physiol. (1998) [Pubmed]
  5. Differential roles of corticotropin-releasing factor receptor subtypes 1 and 2 in opiate withdrawal and in relapse to opiate dependence. Lu, L., Liu, D., Ceng, X., Ma, L. Eur. J. Neurosci. (2000) [Pubmed]
  6. Stress-specific regulation of corticotropin releasing hormone receptor expression in the paraventricular and supraoptic nuclei of the hypothalamus in the rat. Luo, X., Kiss, A., Makara, G., Lolait, S.J., Aguilera, G. J. Neuroendocrinol. (1994) [Pubmed]
  7. Corticotropin-releasing hormone receptor 1 antagonist blocks brain-gut activation induced by colonic distention in rats. Saito, K., Kasai, T., Nagura, Y., Ito, H., Kanazawa, M., Fukudo, S. Gastroenterology (2005) [Pubmed]
  8. Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance. Makrigiannakis, A., Zoumakis, E., Kalantaridou, S., Coutifaris, C., Margioris, A.N., Coukos, G., Rice, K.C., Gravanis, A., Chrousos, G.P. Nat. Immunol. (2001) [Pubmed]
  9. Leptin affects food intake via CRF-receptor-mediated pathways. Gardner, J.D., Rothwell, N.J., Luheshi, G.N. Nat. Neurosci. (1998) [Pubmed]
  10. Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression. Miyata, M., Okada, D., Hashimoto, K., Kano, M., Ito, M. Neuron (1999) [Pubmed]
  11. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Chang, C.P., Pearse, R.V., O'Connell, S., Rosenfeld, M.G. Neuron (1993) [Pubmed]
  12. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Chen, C.Y., Inui, A., Asakawa, A., Fujino, K., Kato, I., Chen, C.C., Ueno, N., Fujimiya, M. Gastroenterology (2005) [Pubmed]
  13. Stress sensitization of ethanol withdrawal-induced reduction in social interaction: inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist. Breese, G.R., Knapp, D.J., Overstreet, D.H. Neuropsychopharmacology (2004) [Pubmed]
  14. Identification and characterization of muscarinic receptors potentiating the stimulation of adenylyl cyclase activity by corticotropin-releasing hormone in membranes of rat frontal cortex. Onali, P., Olianas, M.C. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  15. Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats. Greenwood-Van Meerveld, B., Johnson, A.C., Cochrane, S., Schulkin, J., Myers, D.A. Neurogastroenterol. Motil. (2005) [Pubmed]
  16. Pregnancy decreases immunoreactive parathyroid hormone level in rats with chronic renal failure. Blum, M., Weisman, Y., Turgeman, S., Cabili, S., Wollman, Y., Peer, G., Stern, N., Silverberg, D., Schwartz, D., Iaina, A. Clin. Sci. (1999) [Pubmed]
  17. Corticotropin-releasing factor receptor type 1 is involved in the stress-induced exacerbation of chronic contact dermatitis in rats. Kaneko, K., Kawana, S., Arai, K., Shibasaki, T. Exp. Dermatol. (2003) [Pubmed]
  18. Regulation of corticotropin-releasing hormone receptor messenger ribonucleic acid in the rat brain and pituitary by glucocorticoids and stress. Makino, S., Schulkin, J., Smith, M.A., Pacák, K., Palkovits, M., Gold, P.W. Endocrinology (1995) [Pubmed]
  19. Stress-induced genetic expression of a selective corticotropin-releasing factor-receptor subtype within the rat ovaries: an effect dependent on the ovulatory cycle. Nappi, R.E., Rivest, S. Biol. Reprod. (1995) [Pubmed]
  20. Comparison of central administration of corticotropin-releasing hormone and urocortin on food intake, conditioned taste aversion, and c-Fos expression. Benoit, S.C., Thiele, T.E., Heinrichs, S.C., Rushing, P.A., Blake, K.A., Steeley, R.J. Peptides (2000) [Pubmed]
  21. Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. Chalmers, D.T., Lovenberg, T.W., De Souza, E.B. J. Neurosci. (1995) [Pubmed]
  22. Regulation of corticotropin-releasing factor type 1 (CRF1) receptor messenger ribonucleic acid in the paraventricular nucleus of rat hypothalamus by exogenous CRF. Mansi, J.A., Rivest, S., Drolet, G. Endocrinology (1996) [Pubmed]
  23. Forced swim stress activates rat hippocampal serotonergic neurotransmission involving a corticotropin-releasing hormone receptor-dependent mechanism. Linthorst, A.C., Peñalva, R.G., Flachskamm, C., Holsboer, F., Reul, J.M. Eur. J. Neurosci. (2002) [Pubmed]
  24. Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. Kozicz, T., Yanaihara, H., Arimura, A. J. Comp. Neurol. (1998) [Pubmed]
  25. A centrally acting, anxiolytic angiotensin II AT1 receptor antagonist prevents the isolation stress-induced decrease in cortical CRF1 receptor and benzodiazepine binding. Saavedra, J.M., Armando, I., Bregonzio, C., Juorio, A., Macova, M., Pavel, J., Sanchez-Lemus, E. Neuropsychopharmacology (2006) [Pubmed]
  26. Intracerebroventricular injection of corticotropin-releasing hormone receptor antagonist blocks the suppression of pulsatile luteinizing hormone secretion induced by neuromedin U in ovariectomized rats after 48 hours of fasting. Quan, H., Funabashi, T., Kimura, F. Neurosci. Lett. (2004) [Pubmed]
  27. Involvement of corticotropin-releasing hormone receptor subtypes 1 and 2 in peripheral opioid-mediated inhibition of inflammatory pain. Mousa, S.A., Bopaiah, C.P., Stein, C., Schäfer, M. Pain (2003) [Pubmed]
  28. Enduring, handling-evoked enhancement of hippocampal memory function and glucocorticoid receptor expression involves activation of the corticotropin-releasing factor type 1 receptor. Fenoglio, K.A., Brunson, K.L., Avishai-Eliner, S., Stone, B.A., Kapadia, B.J., Baram, T.Z. Endocrinology (2005) [Pubmed]
  29. Coronary vasodilation and positive inotropism by urocortin in the isolated rat heart. Terui, K., Higashiyama, A., Horiba, N., Furukawa, K.I., Motomura, S., Suda, T. J. Endocrinol. (2001) [Pubmed]
  30. Distribution of corticotropin releasing hormone receptor immunoreactivity in the rat hypothalamus: coexpression in neuropeptide Y and dopamine neurons in the arcuate nucleus. Campbell, R.E., Grove, K.L., Smith, M.S. Brain Res. (2003) [Pubmed]
  31. Effects of corticotropin-releasing hormone receptor antagonists on cocaine-induced dopamine overflow in the medial prefrontal cortex and nucleus accumbens of rats. Gurkovskaya, O.V., Palamarchouk, V., Smagin, G., Goeders, N.E. Synapse (2005) [Pubmed]
  32. Endogenous expression and in vitro study of CRF-related peptides and CRF receptors in the rat gastric antrum. Porcher, C., Peinnequin, A., Pellissier, S., Meregnani, J., Sinniger, V., Canini, F., Bonaz, B. Peptides (2006) [Pubmed]
  33. The role of CRF1 receptors for sympathetic nervous response to laparotomy in anesthetized rats. Uetsuki, N., Segawa, H., Mayahara, T., Fukuda, K. Brain Res. (2005) [Pubmed]
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