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Gene Review

Crh  -  corticotropin releasing hormone

Rattus norvegicus

Synonyms: CRF, Corticoliberin, Corticotropin-releasing factor, Corticotropin-releasing hormone
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Disease relevance of Crh

  • The results also suggest that brain CRF has dual effects on food intake, hyperphagia and anorexia, in a stress-dependent manner [1].
  • When adult obese rats were intracerebroventricularly-treated with ovine corticotropin-releasing hormone (oCRF) for 7 days, they stopped gaining body weight relative to vehicle-infused obese controls [2].
  • The response of plasma ACTH to hypoglycemia was partially inhibited by the administration of CRF-antiserum (CRF-As) or AVP-antiserum (AVP-As) alone, but was found to be completely abolished by the administration of CRF-As + AVP-As as compared to the response in normal rabbit serum-treated rats [3].
  • Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth [4].
  • It is proposed that: 1) hypothalamic NPY may play a role in the establishment and maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) maintenance of the genetic obesity syndrome of the fa/fa rat, and 2) hypothalamic NPY could be partly regulated by central CRF [2].

Psychiatry related information on Crh


High impact information on Crh


Chemical compound and disease context of Crh


Biological context of Crh


Anatomical context of Crh

  • In the light of data that major depression is associated with an activation of brain CRH and LC-NE systems, the time-dependent effect of long-term imipramine administration on decreasing the gene expression of CRH in the hypothalamus and TH in the LC may be relevant to the therapeutic efficacy of this agent in depression [18].
  • These findings suggest that CRH induces skin vascular permeability through NT acting on mast cells and that both peptides should be considered in the pathogenesis of skin disorders exacerbated by stress [20].
  • However, HR rats exhibited higher levels of CRH mRNA in the hypothalamic paraventricular nucleus but lower basal levels in the central nucleus of the amygdala [21].
  • Moreover, B or T MPOA implants also decreased resting-state levels of AVP but not CRH in the median eminence, and these effects were correlated with ACTH responses to restraint [22].
  • The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum [23].

Associations of Crh with chemical compounds


Physical interactions of Crh

  • 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 [27].
  • Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 3',5'-monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase [28].
  • NMU that interacts anatomically and/or functionally with the CRH system is a novel physiological regulator of stress response [7].
  • During atrial pulsation, a stimulus mimicking volume loading and associated with a reduction of systemic ACTH levels, we observed a significant decline in portal concentrations of immunoreactive AVP coupled with a nonsignificant trend toward reduced portal immunoreactive CRF levels [29].
  • CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats [30].

Co-localisations of Crh


Regulatory relationships of Crh

  • CRH induced Fas ligand production and apoptosis [26].
  • Intracerebroventricular BDNF injections (5 microg/rat) in non-anesthetized adult male rats induce a gradual increase in the CRH mRNA signal whereas AVP mRNA signal progressively decreases in the parvocellular and magnocellular PVN portions [31].
  • However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF receptor activation and consequent lower plasma glucocorticoid levels, is unclear [33].
  • 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 [15].
  • Double label staining was also performed to determine if NPY Y1 receptors were expressed in CRH neurons [34].

Other interactions of Crh

  • The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity) [10].
  • This heterogeneous distribution of CRF1 and CRF2 receptor mRNA suggests distinctive functional roles for each receptor in CRF-related systems [27].
  • These results strongly suggest that BDNF could be a stress-responsive intercellular messenger since when it is exogenously administered acts as an important and early component in the activation and recruitment of hypothalamic CRH and AVP neurons [31].
  • This study investigated the effect of CRF on NPY release in vivo, measured by push-pull techniques, in the anesthetized rat [35].
  • Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined [33].

Analytical, diagnostic and therapeutic context of Crh

  • Exposure of ARC/PVN cocultures to the glucocorticoid dexamethasone (DEX) resulted in a dose-dependent increase of CRH secretion and an inhibition of AVP and beta-END; the CRH responses deviated strikingly from predictions based on in vivo experiments [24].
  • Adrenalectomy (ADX) leads to a decrease in the number of CRF-binding sites in the rat anterior pituitary (AP) [36].
  • Acute immobilization caused a significant increase in CRH, but not AVP, mRNA levels in the parvocellular PVN in sham rats [37].
  • The mRNA level was determined by Northern blot analysis using a rat brain CRF-R1 complementary RNA probe [36].
  • When CRF was administered into the PVN via the push-pull cannula at 1 or 5 microg/ml, dose-dependent increases in NPY overflow of two- and fivefold were observed (p < 0.05) [35].


  1. Corticotropin-releasing factor as well as opioid and dopamine are involved in tail-pinch-induced food intake of rats. Samarghandian, S., Ohata, H., Yamauchi, N., Shibasaki, T. Neuroscience (2003) [Pubmed]
  2. Hypothalamic neuropeptide Y messenger ribonucleic acid levels in pre-obese and genetically obese (fa/fa) rats; potential regulation thereof by corticotropin-releasing factor. Bchini-Hooft van Huijsduijnen, O.B., Rohner-Jeanrenaud, F., Jeanrenaud, B. J. Neuroendocrinol. (1993) [Pubmed]
  3. The role of corticotropin-releasing factor and vasopressin in hypoglycemia-induced proopiomelanocortin gene expression in the rat anterior pituitary gland. Suda, T., Nakano, Y., Tozawa, F., Sumitomo, T., Sato, Y., Yamada, M., Demura, H. Brain Res. (1992) [Pubmed]
  4. Elevated corticosterone and inhibition of ACTH responses to CRH and ether in the neonatal rat: effect of hypoxia from birth. Raff, H., Jacobson, L., Cullinan, W.E. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  5. Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. Husum, H., Mathé, A.A. Neuropsychopharmacology (2002) [Pubmed]
  6. Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats. Koban, M., Le, W.W., Hoffman, G.E. Endocrinology (2006) [Pubmed]
  7. A role for neuromedin U in stress response. Hanada, R., Nakazato, M., Murakami, N., Sakihara, S., Yoshimatsu, H., Toshinai, K., Hanada, T., Suda, T., Kangawa, K., Matsukura, S., Sakata, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  8. Spontaneous withdrawal from the triazolobenzodiazepine alprazolam increases cortical corticotropin-releasing factor mRNA expression. Skelton, K.H., Nemeroff, C.B., Owens, M.J. J. Neurosci. (2004) [Pubmed]
  9. Thyrotropin releasing hormone injected into the nucleus accumbens septi selectively increases face grooming in rats. Gargiulo, P.A. Braz. J. Med. Biol. Res. (1996) [Pubmed]
  10. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Vaughan, J., Donaldson, C., Bittencourt, J., Perrin, M.H., Lewis, K., Sutton, S., Chan, R., Turnbull, A.V., Lovejoy, D., Rivier, C. Nature (1995) [Pubmed]
  11. Magnocellular axons in passage through the median eminence release vasopressin. Holmes, M.C., Antoni, F.A., Aguilera, G., Catt, K.J. Nature (1986) [Pubmed]
  12. Co-localization of corticotropin releasing factor and vasopressin mRNA in neurones after adrenalectomy. Wolfson, B., Manning, R.W., Davis, L.G., Arentzen, R., Baldino, F. Nature (1985) [Pubmed]
  13. Corticotropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y. Heinrichs, S.C., Menzaghi, F., Pich, E.M., Hauger, R.L., Koob, G.F. Brain Res. (1993) [Pubmed]
  14. Altered control of the hypothalamo-pituitary-adrenal axis in adult male rats exposed perinatally to food deprivation and/or dehydration. Sebaai, N., Lesage, J., Vieau, D., Alaoui, A., Dupouy, J.P., Deloof, S. Neuroendocrinology (2002) [Pubmed]
  15. 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]
  16. Suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress in a rat model of acute cholestasis. Swain, M.G., Patchev, V., Vergalla, J., Chrousos, G., Jones, E.A. J. Clin. Invest. (1993) [Pubmed]
  17. Hypotensive hemorrhage elevates corticotropin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus. Darlington, D.N., Barraclough, C.A., Gann, D.S. Endocrinology (1992) [Pubmed]
  18. Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. Brady, L.S., Whitfield, H.J., Fox, R.J., Gold, P.W., Herkenham, M. J. Clin. Invest. (1991) [Pubmed]
  19. Corticotropin-releasing hormone causes antidiuresis and antinatriuresis by stimulating vasopressin and inhibiting atrial natriuretic peptide release in male rats. Gutkowska, J., Jankowski, M., Mukaddam-Daher, S., McCann, S.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  20. Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Donelan, J., Boucher, W., Papadopoulou, N., Lytinas, M., Papaliodis, D., Dobner, P., Theoharides, T.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  21. Neurobiological correlates of individual differences in novelty-seeking behavior in the rat: differential expression of stress-related molecules. Kabbaj, M., Devine, D.P., Savage, V.R., Akil, H. J. Neurosci. (2000) [Pubmed]
  22. The inhibitory effect of testosterone on hypothalamic-pituitary-adrenal responses to stress is mediated by the medial preoptic area. Viau, V., Meaney, M.J. J. Neurosci. (1996) [Pubmed]
  23. St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. Butterweck, V., Winterhoff, H., Herkenham, M. Mol. Psychiatry (2001) [Pubmed]
  24. Inherent glucocorticoid response potential of isolated hypothalamic neuroendocrine neurons. Hellbach, S., Gärtner, P., Deicke, J., Fischer, D., Hassan, A.H., Almeida, O.F. FASEB J. (1998) [Pubmed]
  25. Corticotropin-releasing factor, but not arginine vasopressin, stimulates concentration-dependent increases in ACTH secretion from a single corticotrope. Implications for intracellular signals in stimulus-secretion coupling. Canny, B.J., Jia, L.G., Leong, D.A. J. Biol. Chem. (1992) [Pubmed]
  26. Corticotropin-releasing hormone induces Fas ligand production and apoptosis in PC12 cells via activation of p38 mitogen-activated protein kinase. Dermitzaki, E., Tsatsanis, C., Gravanis, A., Margioris, A.N. J. Biol. Chem. (2002) [Pubmed]
  27. 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]
  28. Corticotropin-releasing factor type 1 and type 2alpha receptors regulate phosphorylation of calcium/cyclic adenosine 3',5'-monophosphate response element-binding protein and activation of p42/p44 mitogen-activated protein kinase. Rossant, C.J., Pinnock, R.D., Hughes, J., Hall, M.D., McNulty, S. Endocrinology (1999) [Pubmed]
  29. Evidence for multifactor regulation of the adrenocorticotropin secretory response to hemodynamic stimuli. Plotsky, P.M., Bruhn, T.O., Vale, W. Endocrinology (1985) [Pubmed]
  30. CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats. Heymann-Mönnikes, I., Taché, Y., Trauner, M., Weiner, H., Garrick, T. Brain Res. (1991) [Pubmed]
  31. A single brain-derived neurotrophic factor injection modifies hypothalamo-pituitary-adrenocortical axis activity in adult male rats. Givalois, L., Naert, G., Rage, F., Ixart, G., Arancibia, S., Tapia-Arancibia, L. Mol. Cell. Neurosci. (2004) [Pubmed]
  32. Demonstration of glucocorticoid receptor-like immunoreactivity in glucocorticoid-sensitive vasopressin and corticotropin-releasing factor neurons in the hypothalamic paraventricular nucleus. Uht, R.M., McKelvy, J.F., Harrison, R.W., Bohn, M.C. J. Neurosci. Res. (1988) [Pubmed]
  33. 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]
  34. Corticotropin releasing hormone neurons in the paraventricular nucleus are direct targets for neuropeptide Y neurons in the arcuate nucleus: an anterograde tracing study. Li, C., Chen, P., Smith, M.S. Brain Res. (2000) [Pubmed]
  35. Stimulation of neuropeptide Y overflow in the rat paraventricular nucleus by corticotropin-releasing factor. Morris, M.J., Pavia, J.M. J. Neurochem. (1998) [Pubmed]
  36. Regulation of corticotropin-releasing factor receptor messenger ribonucleic acid in rat anterior pituitary. Sakai, K., Horiba, N., Sakai, Y., Tozawa, F., Demura, H., Suda, T. Endocrinology (1996) [Pubmed]
  37. Increased expression of corticotropin-releasing hormone and vasopressin messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during repeated stress: association with reduction in glucocorticoid receptor mRNA levels. Makino, S., Smith, M.A., Gold, P.W. Endocrinology (1995) [Pubmed]
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