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Gene Review

Ucn  -  urocortin

Mus musculus

Synonyms: Mpv17, Ucn1, Urocortin
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Disease relevance of Ucn


Psychiatry related information on Ucn

  • After food-deprivation, acute intracerebroventricular injection of Ucn suppressed food intake for 1.5 h in wild-type mice [1].
  • This evidence is accumulated along three directions of research: (1) Ucn 1-containing neurons are extremely sensitive to alcohol; (2) the Ucn1 neurocircuit may contribute to the genetic predisposition to high alcohol intake in mice and rats; (3) manipulation of the Ucn1 system alters alcohol consumption and sensitivity [5].
  • Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests [4].
  • Involvement of neurotransmitters in urocortin-induced passive avoidance learning in mice [6].

High impact information on Ucn

  • Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions [4].
  • In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function [4].
  • We also demonstrate that Crhr2 is essential for sustained feeding suppression (hypophagia) induced by Ucn [7].
  • Five daily injections of urocortin significantly lowered body weight and improved glycemic control in ob/ob mice [3].
  • Simultaneous administration of urocortin and CRF receptor antagonist, alpha-helical CRF9-41, blocked the effects of urocortin [3].

Chemical compound and disease context of Ucn


Biological context of Ucn


Anatomical context of Ucn

  • We generated Ucn-deficient mice using embryonic stem cell technology to determine its role in stress-induced behavioral and autonomic responses [8].
  • Neuropeptide depletion of sensory neurons, treatment with the ganglionic blocker hexamethonium, or in situ skin infiltration with the local anesthetic lidocaine did not affect Ucn-induced vascular permeability, indicating that its in situ effect was not mediated through the peripheral nervous system [2].
  • In the present study, we investigated regulation of CRF R2beta levels by Ucn in A7r5 aortic smooth muscle cells [9].
  • Ucn induced accumulation of intracellular cAMP via CRF R2beta in this cell line [9].
  • We had earlier found that urocortin messenger RNA (mRNA) expression within the mouse brain is confined to the region of the Edinger-Westphal (EW) nucleus of the midbrain [10].

Associations of Ucn with chemical compounds


Physical interactions of Ucn


Regulatory relationships of Ucn

  • A 7-day intracerebroventricular infusion of Ucn transiently suppressed ad libitum food intake equally in CRFR1-/- and wild-type mice [1].
  • The increase in Na intake caused by the peripheral infusion of ACTH was blocked by concurrent i.v. infusion of urocortin, substantiating the inhibitory role of this peptide on Na appetite [12].

Other interactions of Ucn

  • Intracerebroventricular injection of CRF or urocortin (Ucn) reduces appetite and body weight [1].
  • By contrast, CRFR1-/- mice did not respond to Ucn 1.5 h after injection [1].
  • Repeated injections of urocortin were continued for 5 days in ob/ob mice [3].
  • Urocortins (Ucns) show different affinities for binding to mCRFR2alpha: Ucn 3 binds mCRFR2alpha with approximately 11-fold lower affinity than Ucn 2, which displays an affinity similar to Ucn 1 (approximately 1 nm) [15].
  • Thus, sites of action of leptin, urocortin, and TNFalpha exist not only in the brain but also at the BBB where they each control the flow of other ingestive signals to CNS targets [16].

Analytical, diagnostic and therapeutic context of Ucn


  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. Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors. Singh, L.K., Boucher, W., Pang, X., Letourneau, R., Seretakis, D., Green, M., Theoharides, T.C. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  3. Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice. Asakawa, A., Inui, A., Ueno, N., Makino, S., Fujino, M.A., Kasuga, M. Gastroenterology (1999) [Pubmed]
  4. Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior. Vetter, D.E., Li, C., Zhao, L., Contarino, A., Liberman, M.C., Smith, G.W., Marchuk, Y., Koob, G.F., Heinemann, S.F., Vale, W., Lee, K.F. Nat. Genet. (2002) [Pubmed]
  5. The urocortin 1 neurocircuit: ethanol-sensitivity and potential involvement in alcohol consumption. Ryabinin, A.E., Weitemier, A.Z. Brain Res. Brain Res. Rev. (2006) [Pubmed]
  6. Involvement of neurotransmitters in urocortin-induced passive avoidance learning in mice. Telegdy, G., Tiricz, H., Adamik, A. Brain Res. Bull. (2005) [Pubmed]
  7. 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]
  8. Urocortin-deficient mice display normal stress-induced anxiety behavior and autonomic control but an impaired acoustic startle response. Wang, X., Su, H., Copenhagen, L.D., Vaishnav, S., Pieri, F., Shope, C.D., Brownell, W.E., De Biasi, M., Paylor, R., Bradley, A. Mol. Cell. Biol. (2002) [Pubmed]
  9. Regulation of corticotropin-releasing factor receptor type 2beta mRNA via cyclic AMP pathway in A7r5 aortic smooth muscle cells. Kageyama, K., Gaudriault, G.E., Suda, T., Vale, W.W. Cell. Signal. (2003) [Pubmed]
  10. Urocortin expression in the Edinger-Westphal nucleus is up-regulated by stress and corticotropin-releasing hormone deficiency. Weninger, S.C., Peters, L.L., Majzoub, J.A. Endocrinology (2000) [Pubmed]
  11. Vasodilative effects of urocortin II via protein kinase A and a mitogen-activated protein kinase in rat thoracic aorta. Kageyama, K., Furukawa, K., Miki, I., Terui, K., Motomura, S., Suda, T. J. Cardiovasc. Pharmacol. (2003) [Pubmed]
  12. The inhibitory effect of hormones associated with stress on Na appetite of sheep. Weisinger, R.S., Blair-West, J.R., Burns, P., Denton, D.A., McKinley, M.J., Purcell, B., Vale, W., Rivier, J., Sunagawa, K. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  13. 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]
  14. Activation of urocortin transport into brain by leptin. Kastin, A.J., Akerstrom, V., Pan, W. Peptides (2000) [Pubmed]
  15. 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]
  16. Modulation of feeding-related peptide/protein signals by the blood-brain barrier. Pan, W., Akerstrom, V., Zhang, J., Pejovic, V., Kastin, A.J. J. Neurochem. (2004) [Pubmed]
  17. Corticotropin-releasing hormone receptor 2-deficient mice have reduced intestinal inflammatory responses. Kokkotou, E., Torres, D., Moss, A.C., O'Brien, M., Grigoriadis, D.E., Karalis, K., Pothoulakis, C. J. Immunol. (2006) [Pubmed]
  18. The structures of the mouse and human urocortin genes (Ucn and UCN). Zhao, L., Donaldson, C.J., Smith, G.W., Vale, W.W. Genomics (1998) [Pubmed]
  19. Urocortin reduces oxygen consumption in lean and ob/ob mice. Asakawa, A., Inui, A., Ueno, N., Makino, S., Fujimiya, M., Fujino, M.A., Kasuga, M. Int. J. Mol. Med. (2001) [Pubmed]
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