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Urocortin is a protein which belongs to the corticotropin-releasing factor (CRF) family of proteins which includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response. In humans, urocortin is encoded by the UCN gene.[1][2][3]

Structure, Localization, and Interactions[edit]

Urocortin is a peptide composed of 40 amino acids. Urocortin is composed of a single alpha helix structure. The human UCN gene contains two exons, and the entirety of the coding region is contained within the second exon[4]. Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF[5]. Areas of similarity between urocortin and CRF expression include the supraoptic nucleus and the hippocampus[6][7]. Urocortin is also expressed in areas distinct from CRF expression; these areas notably include the median eminence, the Edinger-Westphal nucleus, and the sphenoid nucleus[7]. Additionally, Urocortin is expressed in peripheral tissues such as the heart[8].

Urocortin is known to interact both with the CRF type 1 and CRF type 2 receptors[9][10][11]. Furthermore, Urocortin is thought to be the primary ligand for the CRF type 2 receptor, as it has higher binding affinity for the CRF type 2 receptor than CRF[9]. Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain[12].

Stress Response and Social Behavior[edit]

Urocortin is closely related to CRF, which mediates the mammalian stress response. Urocortin is consequently implicated in a number of stress responses, primarily relating to appetite and food intake. Administration of urocortin to the central nervous system of mice and rats has been shown to decrease appetite[13]. Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats[13]. These general anxiety-linked behaviors are likely induced through the CRF type 1 receptor, and the appetite behaviors are likely induced through the CRF type 2 receptor. The reduction in appetite from urocortin treatment could be a result of suppression of gastric emptying and/or hypoglycemia, which have been shown to result from urocortin treatment[14]. Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in the supraoptic nucleus[15].

Montane Voles and Meadow Voles are closely related species of voles which are regularly studied as a model for social and mating behavior. The distribution of urocortin-expressing neurons differs in meadow voles compared to montane voles, suggesting urocortin may also play a role in modulating social behavior in some species[16].

Cardiovascular Effects[edit]

Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally[8]. These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in the cardiac atria and ventricles[17]. Urocortin also functions to protect cardiovascular tissue from ischemic injury[18]. Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.

In Non-Mammals[edit]

Urocortin is not present in all non-mammals; the closet analogue in teleost fish is urotensin I[19]. However, in amphibian species such as Xenopus laevis, urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin in Xenopus has been shown to increase cAMP accumulation and inhibit appetite[19].

  1. ^ Zhao L, Donaldson CJ, Smith GW, Vale WW (April 1999). "The structures of the mouse and human urocortin genes (Ucn and UCN)". Genomics. 50 (1): 23–33. doi:10.1006/geno.1998.5292. PMID 9628819.
  2. ^ Tsarev OB (July 1977). "[Dynamics of matrix synthesis in molecular biophysics. II. Principle of insertability and the single-valued solution of feedback tasks]". Biofizika. 22 (2): 197–200. PMID 861256.
  3. ^ "Entrez Gene: UCN urocortin".
  4. ^ Zhao, Lingyun; Donaldson, Cynthia J.; Smith, George W.; Vale, Wylie W. (1998-05-15). "The Structures of the Mouse and Human Urocortin Genes (Ucn and UCN)". Genomics. 50 (1): 23–33. doi:10.1006/geno.1998.5292.
  5. ^ Furman, Brian L. (2007-01-01). xPharm: The Comprehensive Pharmacology Reference. New York: Elsevier. pp. 1–2. ISBN 9780080552323.
  6. ^ Smagin, Gennady N; Heinrichs, Stephen C; Dunn, Adrian J (2001-05-01). "The role of CRH in behavioral responses to stress". Peptides. 22 (5): 713–724. doi:10.1016/S0196-9781(01)00384-9.
  7. ^ a b Morin, S. M.; Ling, N.; Liu, X. -J.; Kahl, S. D.; Gehlert, D. R. (1999-08-01). "Differential distribution of urocortin- and corticotropin-releasing factor-like immunoreactivities in the rat brain". Neuroscience. 92 (1): 281–291. doi:10.1016/S0306-4522(98)00732-5.
  8. ^ a b Latchman, David S. (2002-08-01). "Urocortin". The International Journal of Biochemistry & Cell Biology. 34 (8): 907–910. ISSN 1357-2725. PMID 12007627.
  9. ^ a b Vaughan, J.; Donaldson, C.; Bittencourt, J.; Perrin, M. H.; Lewis, K.; Sutton, S.; Chan, R.; Turnbull, A. V.; Lovejoy, D. (1995-11-16). "Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor". Nature. 378 (6554): 287–292. doi:10.1038/378287a0. ISSN 0028-0836. PMID 7477349.
  10. ^ Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (October 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin". Neuropharmacology. 36 (10): 1439–46. doi:10.1016/S0028-3908(97)00098-1. PMID 9423932.
  11. ^ Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (May 1996). "Cloning and characterization of human urocortin". Endocrinology. 137 (5): 2167–70. doi:10.1210/en.137.5.2167. PMID 8612563.
  12. ^ Baigent, S M (2000). "Urocortin is the principal ligand for the corticotrophin- releasing factor binding protein in the ovine brain with no evidence for a sauvagine-like peptide" (PDF). Journal of Molecular Endocrinology. 24: 53–63.
  13. ^ a b Skelton, Kelly H; Owens, Michael J; Nemeroff, Charles B (2000-09-25). "The neurobiology of urocortin". Regulatory Peptides. 20th Anniversary Celebratory Special Issue. 93 (1–3): 85–92. doi:10.1016/S0167-0115(00)00180-4.
  14. ^ Stengel, Andreas; Taché, Yvette France (2014-01-01). "CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress". Neuroendocrine Science. 8: 52. doi:10.3389/fnins.2014.00052. PMC 3957495. PMID 24672423.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ Hara, Yuko; Ueta, Yoichi; Isse, Toyohi; Kabashima, Narutoshi; Shibuya, Izumi; Hattori, Yukio; Yamashita, Hiroshi (1997-06-20). "Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation". Neuroscience Letters. 229 (1): 65–68. doi:10.1016/S0304-3940(97)00419-9.
  16. ^ Lim, Miranda M.; Tsivkovskaia, Natalia O.; Bai, Yaohui; Young, Larry J.; Ryabinin, Andrey E. (2006-01-01). "Distribution of Corticotropin-releasing factor and Urocortin 1 in the vole brain". Brain, behavior and evolution. 68 (4): 229–240. doi:10.1159/000094360. ISSN 0006-8977. PMC 1828133. PMID 16816534.
  17. ^ Kishimoto, T.; Pearse, R. V.; Lin, C. R.; Rosenfeld, M. G. (1995-02-14). "A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle". Proceedings of the National Academy of Sciences of the United States of America. 92 (4): 1108–1112. ISSN 0027-8424. PMC 42647. PMID 7755719.
  18. ^ Brar, B. K.; Jonassen, A. K.; Stephanou, A.; Santilli, G.; Railson, J.; Knight, R. A.; Yellon, D. M.; Latchman, D. S. (2000-03-24). "Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway". The Journal of Biological Chemistry. 275 (12): 8508–8514. ISSN 0021-9258. PMID 10722688.
  19. ^ a b Boorse, Graham C.; Crespi, Erica J.; Dautzenberg, Frank M.; Denver, Robert J. "Urocortins of the South African Clawed Frog,Xenopus laevis: Conservation of Structure and Function in Tetrapod Evolution". Endocrinology. 146 (11): 4851–4860. doi:10.1210/en.2005-0497.
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