Urocortin: Difference between revisions

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{{Infobox gene}}
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'''Urocortin''' is a [[protein]] that in humans is encoded by the ''UCN'' [[gene]]. Urocortin belongs to the [[corticotropin-releasing factor]] (CRF) family of proteins which includes [[Corticotropin-releasing hormone|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.<ref name="pmid96288192">{{cite journal | vauthors = Zhao L, Donaldson CJ, Smith GW, Vale WW | title = The structures of the mouse and human urocortin genes (Ucn and UCN) | journal = Genomics | volume = 50 | issue = 1 | pages = 23–33 | date = May 1998 | pmid = 9628819 | pmc =  | doi = 10.1006/geno.1998.5292 }}</ref><ref name="pmid8612562">{{cite journal | vauthors = Tsarev OB | title = [Dynamics of matrix synthesis in molecular biophysics. II. Principle of insertability and the single-valued solution of feedback tasks] | journal = Biofizika | volume = 22 | issue = 2 | pages = 197–200 | date = July 1977 | pmid = 861256 | pmc = | doi =  }}</ref><ref name="entrez2">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7349|title=Entrez Gene: UCN urocortin|accessdate=}}</ref>
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Urocortin
| HGNCid = 12516
| Symbol = UCN
| AltSymbols =; MGC129974; MGC129975; UI; UROC
| OMIM = 600945
| ECnumber =
  | Homologene = 2515
| MGIid = 1276123
| GeneAtlas_image1 = PBB_GE_UCN_206072_at_tn.png
| Function = {{GNF_GO|id=GO:0005184 |text = neuropeptide hormone activity}}  
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}}
| Process = {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7349
    | Hs_Ensembl = ENSG00000163794
    | Hs_RefseqProtein = NP_003344
    | Hs_RefseqmRNA = NM_003353
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 27383769
    | Hs_GenLoc_end = 27384634
    | Hs_Uniprot = P55089
    | Mm_EntrezGene = 22226
    | Mm_Ensembl = ENSMUSG00000038676
    | Mm_RefseqmRNA = NM_021290
    | Mm_RefseqProtein = NP_067265
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 31414570
    | Mm_GenLoc_end = 31415476
    | Mm_Uniprot = Q14A76
  }}
}}
'''Urocortin''', also known as '''UCN''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: UCN urocortin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7349| accessdate = }}</ref>
<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = This gene is a member of the sauvagine/corticotropin-releasing factor/urotensin I family. It is structurally related to the corticotropin-releasing factor (CRF) gene and the encoded product is an endogenous ligand for CRF type 2 receptors. In the brain it may be responsible for the effects of stress on appetite. In spite of the gene family name similarity, the product of this gene has no sequence similarity to urotensin II.<ref name="entrez">{{cite web | title = Entrez Gene: UCN urocortin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7349| accessdate = }}</ref>
}}
Urocortin is a potent [[anorexigenic]] [[peptide]] of 40 [[amino acid]]s that induces fed-like motor activity when administered centrally or peripherally in fasted animals. Urocortin belongs to the [[corticotropin-releasing factor]] (CRF) family that includes [[Corticotropin-releasing hormone|CRF]], [[urotensin I]], [[sauvagine]], [[urocortin II]] and [[urocortin III]]. Urocortin is also a potent and long-lasting [[hypotensive]] agent and increases [[coronary blood flow]].


==References==
== Structure, localization, and interactions ==
{{reflist|2}}
Urocortin is a [[peptide]] composed of 40 [[amino acid]]s. 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.<ref>{{cite journal | vauthors = Zhao L, Donaldson CJ, Smith GW, Vale WW | title = The structures of the mouse and human urocortin genes (Ucn and UCN) | journal = Genomics | volume = 50 | issue = 1 | pages = 23–33 | date = May 1998 | pmid = 9628819 | doi = 10.1006/geno.1998.5292 }}</ref> Urocortin is expressed widely in the central and peripheral nervous systems, with a pattern similar to that of CRF.<ref>{{cite book | doi = 10.1016/B978-008055232-3.62835-1 | title = xPharm: The Comprehensive Pharmacology Reference | last = Furman | first = Brian L. | name-list-format = vanc | date = 2007-01-01 | publisher = Elsevier | isbn = 978-0-08-055232-3 | location = New York | pages = 1–2 }}</ref> Areas of similarity between urocortin and CRF expression include the [[supraoptic nucleus]] and the [[hippocampus]].<ref name="pmid11337084">{{cite journal | vauthors = Smagin GN, Heinrichs SC, Dunn AJ | title = The role of CRH in behavioral responses to stress | journal = Peptides | volume = 22 | issue = 5 | pages = 713–24 | year = 2001 | pmid = 11337084 | doi = 10.1016/S0196-9781(01)00384-9 }}</ref><ref name="Morin_1999">{{cite journal | vauthors = Morin SM, Ling N, Liu XJ, Kahl SD, Gehlert DR | title = Differential distribution of urocortin- and corticotropin-releasing factor-like immunoreactivities in the rat brain | journal = Neuroscience | volume = 92 | issue = 1 | pages = 281–91 | year = 1999 | pmid = 10392850 | doi = 10.1016/S0306-4522(98)00732-5 }}</ref> Urocortin is also expressed in areas distinct from CRF expression; these areas notably include the [[median eminence]], the [[Edinger–Westphal nucleus|Edinger-Westphal nucleus]], and the sphenoid nucleus.<ref name="Morin_1999" /> Additionally, Urocortin is expressed in peripheral tissues such as the heart.<ref name="Latchman_2002">{{cite journal | vauthors = Latchman DS | title = Urocortin | journal = The International Journal of Biochemistry & Cell Biology | volume = 34 | issue = 8 | pages = 907–10 | date = August 2002 | pmid = 12007627 | doi = 10.1016/S1357-2725(02)00011-0 }}</ref>
==Further reading==
 
{{refbegin | 2}}
Urocortin is known to interact both with the [[Corticotropin-releasing hormone receptor 1|CRF type 1]] and [[Corticotropin releasing hormone receptor 2|CRF type 2]] receptors.<ref name="Vaughan_1995">{{cite journal | vauthors = Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C | title = Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor | journal = Nature | volume = 378 | issue = 6554 | pages = 287–92 | date = November 1995 | pmid = 7477349 | doi = 10.1038/378287a0 }}</ref><ref name="pmid94239322">{{cite journal | vauthors = Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ | title = Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin | journal = Neuropharmacology | volume = 36 | issue = 10 | pages = 1439–46 | date = October 1997 | pmid = 9423932 | doi = 10.1016/S0028-3908(97)00098-1 }}</ref><ref name="pmid86125632">{{cite journal | vauthors = Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW | title = Cloning and characterization of human urocortin | journal = Endocrinology | volume = 137 | issue = 5 | pages = 2167–70 | date = May 1996 | pmid = 8612563 | doi = 10.1210/en.137.5.2167 }}</ref> 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.<ref name="Vaughan_1995" /> Additionally, urocortin interacts with CRF Binding Protein in the mammalian brain.<ref name="pmid10656997">{{cite journal | vauthors = Baigent SM, Lowry PJ | title = Urocortin is the principal ligand for the corticotrophin-releasing factor binding protein in the ovine brain with no evidence for a sauvagine-like peptide | journal = Journal of Molecular Endocrinology | volume = 24 | issue = 1 | pages = 53–63 | year = 2000 | pmid = 10656997 | doi = 10.1677/jme.0.0240053 }}</ref>
*Inui, Bowers, et al. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ. FASEB J. 2004 Mar;18(3):439-56. [http://www.fasebj.org/cgi/content/full/18/3/439  PMID: 15003990]
 
*Huang Y, Yao XQ, Lau CW, Chan YC, Tsang SY, Chan FL. Urocortin and cardiovascular protection. Acta Pharmacol Sin. 2004 Mar;25(3):257-65.
== Stress response and social behavior ==
*Takahashi, Kazuhiro.  Translational medicine in fish-derived peptides: From fish endocrinology to human physiology and diseases.   Endocrine Journal (Kyoto, Japan)  (2004),  51(1),  1-17.
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.<ref name="Skelton_2000">{{cite journal | vauthors = Skelton KH, Owens MJ, Nemeroff CB | title = The neurobiology of urocortin | journal = Regulatory Peptides | volume = 93 | issue = 1-3 | pages = 85–92 | year = 2000 | pmid = 11033056 | doi = 10.1016/S0167-0115(00)00180-4 }}</ref> Additionally, central urocortin treatment increases anxiety-linked behaviors and increases motor activity in mice and rats.<ref name="Skelton_2000" /> 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.<ref>{{cite journal | vauthors = Stengel A, Taché Y | title = CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress | journal = Frontiers in Neuroscience | volume = 8 | pages = 52 | date = 2014-01-01 | pmid = 24672423 | pmc = 3957495 | doi = 10.3389/fnins.2014.00052 }}</ref> Urocortin expression is stimulated in response to osmotic stress; water deprivation in rats has been shown to induce urocortin expression in the [[supraoptic nucleus]].<ref>{{cite journal | vauthors = Hara Y, Ueta Y, Isse T, Kabashima N, Shibuya I, Hattori Y, Yamashita H | title = Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation | journal = Neuroscience Letters | volume = 229 | issue = 1 | pages = 65–8 | year = 1997 | pmid = 9224803 | doi = 10.1016/S0304-3940(97)00419-9 }}</ref>
{{PBB_Further_reading
 
| citations =  
[[Montane vole|Montane Voles]] and [[Meadow vole|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.<ref>{{cite journal | vauthors = Lim MM, Tsivkovskaia NO, Bai Y, Young LJ, Ryabinin AE | title = Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain | journal = Brain, Behavior and Evolution | volume = 68 | issue = 4 | pages = 229–40 | date = 2006-01-01 | pmid = 16816534 | pmc = 1828133 | doi = 10.1159/000094360 }}</ref>
*{{cite journal  | author=Tsarev OB |title=[Dynamics of matrix synthesis in molecular biophysics. II. Principle of insertability and the single-valued solution of feedback tasks] |journal=Biofizika |volume=22 |issue= 2 |pages= 197-200 |year= 1977 |pmid= 861256 |doi= }}
 
*{{cite journal | author=Donaldson CJ, Sutton SW, Perrin MH, ''et al.'' |title=Cloning and characterization of human urocortin. |journal=Endocrinology |volume=137 |issue= 5 |pages= 2167-70 |year= 1996 |pmid= 8612563 |doi= }}
== Cardiovascular effects ==
*{{cite journal | author=Adachi T, Schamel WW, Kim KM, ''et al.'' |title=The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence. |journal=EMBO J. |volume=15 |issue= 7 |pages= 1534-41 |year= 1996 |pmid= 8612576 |doi= }}
Urocortin has been shown to induce increases in heart rate and coronary blood flow when applied peripherally.<ref name="Latchman_2002" /> These effects are likely mediated through the CRF type 2 receptor, as this receptor is found in the [[Heart|cardiac atria]] and ventricles.<ref>{{cite journal | vauthors = Kishimoto T, Pearse RV, Lin CR, Rosenfeld MG | title = A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 4 | pages = 1108–12 | date = February 1995 | pmid = 7755719 | pmc = 42647 | doi = 10.1073/pnas.92.4.1108 }}</ref> Urocortin also functions to protect cardiovascular tissue from [[Ischemia|ischemic]] injury.<ref>{{cite journal | vauthors = Brar BK, Jonassen AK, Stephanou A, Santilli G, Railson J, Knight RA, Yellon DM, Latchman DS | title = Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway | journal = The Journal of Biological Chemistry | volume = 275 | issue = 12 | pages = 8508–14 | date = March 2000 | pmid = 10722688 | doi = 10.1074/jbc.275.12.8508 }}</ref> Urocortin's cardiovascular effects separate it from other members of the CRF family, and likely represent its primary biological function.
*{{cite journal  | author=Iino K, Sasano H, Oki Y, ''et al.'' |title=Urocortin expression in human pituitary gland and pituitary adenoma. |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue= 11 |pages= 3842-50 |year= 1997 |pmid= 9360550 |doi= }}
 
*{{cite journal  | author=Gottowik J, Goetschy V, Henriot S, ''et al.'' |title=Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin. |journal=Neuropharmacology |volume=36 |issue= 10 |pages= 1439-46 |year= 1998 |pmid= 9423932 |doi= }}
== In non-mammals ==
*{{cite journal | author=Bamberger CM, Wald M, Bamberger AM, ''et al.'' |title=Human lymphocytes produce urocortin, but not corticotropin-releasing hormone. |journal=J. Clin. Endocrinol. Metab. |volume=83 |issue= 2 |pages= 708-11 |year= 1998 |pmid= 9467598 |doi= }}
Urocortin is not present in all non-mammals; the closet analogue in [[teleost]] fish is urotensin I.<ref name="Boorse_2005">{{cite journal | vauthors = Boorse GC, Crespi EJ, Dautzenberg FM, Denver RJ | title = Urocortins of the South African clawed frog, Xenopus laevis: conservation of structure and function in tetrapod evolution | journal = Endocrinology | volume = 146 | issue = 11 | pages = 4851–60 | date = November 2005 | pmid = 16037378 | doi = 10.1210/en.2005-0497 }}</ref> However, in amphibian species such as ''[[African clawed frog|Xenopus laevis]]'', urocortin is expressed in tissues such as brain, pituitary, kidney, heart, and skin. Urocortin in ''Xenopus'' has been shown to increase [[Cyclic adenosine monophosphate|cAMP]] accumulation and inhibit appetite<ref name="Boorse_2005" />
*{{cite journal | author=Takahashi K, Totsune K, Sone M, ''et al.'' |title=Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain. |journal=Peptides |volume=19 |issue= 4 |pages= 643-7 |year= 1998 |pmid= 9622018 |doi= }}
 
*{{cite journal  | author=Zhao L, Donaldson CJ, Smith GW, Vale WW |title=The structures of the mouse and human urocortin genes (Ucn and UCN). |journal=Genomics |volume=50 |issue= 1 |pages= 23-33 |year= 1999 |pmid= 9628819 |doi= 10.1006/geno.1998.5292 }}
== References ==
*{{cite journal  | author=Iino K, Sasano H, Oki Y, ''et al.'' |title=Urocortin expression in the human central nervous system. |journal=Clin. Endocrinol. (Oxf) |volume=50 |issue= 1 |pages= 107-14 |year= 1999 |pmid= 10341863 |doi= }}
{{reflist|33em}}
*{{cite journal  | author=Watanabe F, Oki Y, Ozawa M, ''et al.'' |title=Urocortin in human placenta and maternal plasma. |journal=Peptides |volume=20 |issue= 2 |pages= 205-9 |year= 1999 |pmid= 10422876 |doi= }}
 
*{{cite journal | author=Slominski A, Roloff B, Curry J, ''et al.'' |title=The skin produces urocortin. |journal=J. Clin. Endocrinol. Metab. |volume=85 |issue= 2 |pages= 815-23 |year= 2000 |pmid= 10690896 |doi= }}
== Further reading ==
*{{cite journal  | author=Muramatsu Y, Fukushima K, Iino K, ''et al.'' |title=Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa. |journal=Peptides |volume=21 |issue= 12 |pages= 1799-809 |year= 2001 |pmid= 11150640 |doi= }}
{{refbegin|33em}}
*{{cite journal  | author=Muramatsu Y, Sugino N, Suzuki T, ''et al.'' |title=Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries. |journal=J. Clin. Endocrinol. Metab. |volume=86 |issue= 3 |pages= 1362-9 |year= 2001 |pmid= 11238533 |doi= }}
* {{cite journal | vauthors = Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M | title = Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ | journal = FASEB Journal | volume = 18 | issue = 3 | pages = 439–56 | date = March 2004 | pmid = 15003990 | doi = 10.1096/fj.03-0641rev }}
*{{cite journal  | author=Hsu SY, Hsueh AJ |title=Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. |journal=Nat. Med. |volume=7 |issue= 5 |pages= 605-11 |year= 2001 |pmid= 11329063 |doi= 10.1038/87936 }}
* {{cite journal | vauthors = Huang Y, Yao XQ, Lau CW, Chan YC, Tsang SY, Chan FL | date = Mar 2004 | title = Urocortin and cardiovascular protection | journal = Acta Pharmacol Sin. | volume = 25 | issue = 3| pages = 257–65 }}
*{{cite journal | author=Lewis K, Li C, Perrin MH, ''et al.'' |title=Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 13 |pages= 7570-5 |year= 2001 |pmid= 11416224 |doi= 10.1073/pnas.121165198 }}
* {{cite journal | vauthors = Takahashi, Kazuhiro | year = 2004 | title = Translational medicine in fish-derived peptides: From fish endocrinology to human physiology and diseases | journal = Endocrine Journal (Kyoto, Japan) | volume = 51 | issue = 1| pages = 1–17 | doi=10.1507/endocrj.51.1}}
*{{cite journal | author=Kimura Y, Takahashi K, Totsune K, ''et al.'' |title=Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue= 1 |pages= 340-6 |year= 2002 |pmid= 11788672 |doi= }}
* {{cite journal | vauthors = Adachi T, Schamel WW, Kim KM, Watanabe T, Becker B, Nielsen PJ, Reth M | title = The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence | journal = The EMBO Journal | volume = 15 | issue = 7 | pages = 1534–41 | date = April 1996 | pmid = 8612576 | pmc = 450061 | doi =  }}
*{{cite journal  | author=Florio P, Arcuri F, Ciarmela P, ''et al.'' |title=Identification of urocortin mRNA and peptide in the human endometrium. |journal=J. Endocrinol. |volume=173 |issue= 2 |pages= R9-14 |year= 2002 |pmid= 12010647 |doi=  }}
* {{cite journal | vauthors = Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T | title = Urocortin expression in human pituitary gland and pituitary adenoma | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 82 | issue = 11 | pages = 3842–50 | date = November 1997 | pmid = 9360550 | doi = 10.1210/jc.82.11.3842 }}
*{{cite journal | author=Arcuri F, Cintorino M, Florio P, ''et al.'' |title=Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma. |journal=Prostate |volume=52 |issue= 3 |pages= 167-72 |year= 2002 |pmid= 12111693 |doi= 10.1002/pros.10094 }}
* {{cite journal | vauthors = Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ | title = Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin | journal = Neuropharmacology | volume = 36 | issue = 10 | pages = 1439–46 | date = October 1997 | pmid = 9423932 | doi = 10.1016/S0028-3908(97)00098-1 }}
*{{cite journal | author=Ikeda K, Tojo K, Oki Y, Nakao K |title=Urocortin has cell-proliferative effects on cardiac non-myocytes. |journal=Life Sci. |volume=71 |issue= 16 |pages= 1929-38 |year= 2002 |pmid= 12175707 |doi=  }}
* {{cite journal | vauthors = Bamberger CM, Wald M, Bamberger AM, Ergün S, Beil FU, Schulte HM | title = Human lymphocytes produce urocortin, but not corticotropin-releasing hormone | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 83 | issue = 2 | pages = 708–11 | date = February 1998 | pmid = 9467598 | doi = 10.1210/jc.83.2.708 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Takahashi K, Totsune K, Sone M, Murakami O, Satoh F, Arihara Z, Sasano H, Iino K, Mouri T | title = Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain | journal = Peptides | volume = 19 | issue = 4 | pages = 643–7 | year = 1998 | pmid = 9622018 | doi = 10.1016/S0196-9781(98)00012-6 }}
}}
* {{cite journal | vauthors = Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Takahashi K, Suzuki H, Tezuka F, Yoshimi T, Nagura H | title = Urocortin expression in the human central nervous system | journal = Clinical Endocrinology | volume = 50 | issue = 1 | pages = 107–14 | date = January 1999 | pmid = 10341863 | doi = 10.1046/j.1365-2265.1999.00624.x }}
* {{cite journal | vauthors = Watanabe F, Oki Y, Ozawa M, Masuzawa M, Iwabuchi M, Yoshimi T, Nishiguchi T, Iino K, Sasano H | title = Urocortin in human placenta and maternal plasma | journal = Peptides | volume = 20 | issue = 2 | pages = 205–9 | year = 1999 | pmid = 10422876 | doi = 10.1016/S0196-9781(98)00175-2 }}
* {{cite journal | vauthors = Slominski A, Roloff B, Curry J, Dahiya M, Szczesniewski A, Wortsman J | title = The skin produces urocortin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 85 | issue = 2 | pages = 815–23 | date = February 2000 | pmid = 10690896 | doi = 10.1210/jc.85.2.815 }}
* {{cite journal | vauthors = Muramatsu Y, Fukushima K, Iino K, Totsune K, Takahashi K, Suzuki T, Hirasawa G, Takeyama J, Ito M, Nose M, Tashiro A, Hongo M, Oki Y, Nagura H, Sasano H | title = Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa | journal = Peptides | volume = 21 | issue = 12 | pages = 1799–809 | date = December 2000 | pmid = 11150640 | doi = 10.1016/S0196-9781(00)00335-1 }}
* {{cite journal | vauthors = Muramatsu Y, Sugino N, Suzuki T, Totsune K, Takahashi K, Tashiro A, Hongo M, Oki Y, Sasano H | title = Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 3 | pages = 1362–9 | date = March 2001 | pmid = 11238533 | doi = 10.1210/jc.86.3.1362 }}
* {{cite journal | vauthors = Hsu SY, Hsueh AJ | title = Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor | journal = Nature Medicine | volume = 7 | issue = 5 | pages = 605–11 | date = May 2001 | pmid = 11329063 | doi = 10.1038/87936 }}
* {{cite journal | vauthors = Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW | title = Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 13 | pages = 7570–5 | date = June 2001 | pmid = 11416224 | pmc = 34709 | doi = 10.1073/pnas.121165198 }}
* {{cite journal | vauthors = Kimura Y, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Darnel AD, Suzuki T, Ebina M, Nukiwa T, Sasano H | title = Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 87 | issue = 1 | pages = 340–6 | date = January 2002 | pmid = 11788672 | doi = 10.1210/jc.87.1.340 }}
* {{cite journal | vauthors = Florio P, Arcuri F, Ciarmela P, Runci Y, Romagnoli R, Cintorino M, Di Blasio AM, Petraglia F | title = Identification of urocortin mRNA and peptide in the human endometrium | journal = The Journal of Endocrinology | volume = 173 | issue = 2 | pages = R9-14 | date = May 2002 | pmid = 12010647 | doi = 10.1677/joe.0.173R009 }}
* {{cite journal | vauthors = Arcuri F, Cintorino M, Florio P, Floccari F, Pergola L, Romagnoli R, Petraglia F, Tosi P, Teresa Del Vecchio M | title = Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma | journal = The Prostate | volume = 52 | issue = 3 | pages = 167–72 | date = August 2002 | pmid = 12111693 | doi = 10.1002/pros.10094 }}
* {{cite journal | vauthors = Ikeda K, Tojo K, Oki Y, Nakao K | title = Urocortin has cell-proliferative effects on cardiac non-myocytes | journal = Life Sciences | volume = 71 | issue = 16 | pages = 1929–38 | date = September 2002 | pmid = 12175707 | doi = 10.1016/S0024-3205(02)01945-8 }}
{{refend}}
{{refend}}


{{Signaling peptide/protein receptor modulators}}


[[Category:Hormones]]
[[Category:Corticotropin-releasing hormone receptor agonists]]
[[de:Urocortin]]
[[Category:Peptide hormones]]
{{biochem-stub}}
{{protein-stub}}
{{WikiDoc Sources}}

Latest revision as of 19:51, 18 March 2018

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Urocortin is a protein that in humans is encoded by the UCN gene. Urocortin 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.[1][2][3]

Structure, localization, and interactions

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

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

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

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]

References

  1. ↑ Zhao L, Donaldson CJ, Smith GW, Vale WW (May 1998). "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 L, Donaldson CJ, Smith GW, Vale WW (May 1998). "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.
  5. ↑ Furman BL (2007-01-01). xPharm: The Comprehensive Pharmacology Reference. New York: Elsevier. pp. 1–2. doi:10.1016/B978-008055232-3.62835-1. ISBN 978-0-08-055232-3.
  6. ↑ Smagin GN, Heinrichs SC, Dunn AJ (2001). "The role of CRH in behavioral responses to stress". Peptides. 22 (5): 713–24. doi:10.1016/S0196-9781(01)00384-9. PMID 11337084.
  7. ↑ 7.0 7.1 Morin SM, Ling N, Liu XJ, Kahl SD, Gehlert DR (1999). "Differential distribution of urocortin- and corticotropin-releasing factor-like immunoreactivities in the rat brain". Neuroscience. 92 (1): 281–91. doi:10.1016/S0306-4522(98)00732-5. PMID 10392850.
  8. ↑ 8.0 8.1 Latchman DS (August 2002). "Urocortin". The International Journal of Biochemistry & Cell Biology. 34 (8): 907–10. doi:10.1016/S1357-2725(02)00011-0. PMID 12007627.
  9. ↑ 9.0 9.1 Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C (November 1995). "Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor". Nature. 378 (6554): 287–92. doi:10.1038/378287a0. 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 SM, Lowry PJ (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". Journal of Molecular Endocrinology. 24 (1): 53–63. doi:10.1677/jme.0.0240053. PMID 10656997.
  13. ↑ 13.0 13.1 Skelton KH, Owens MJ, Nemeroff CB (2000). "The neurobiology of urocortin". Regulatory Peptides. 93 (1–3): 85–92. doi:10.1016/S0167-0115(00)00180-4. PMID 11033056.
  14. ↑ Stengel A, Taché Y (2014-01-01). "CRF and urocortin peptides as modulators of energy balance and feeding behavior during stress". Frontiers in Neuroscience. 8: 52. doi:10.3389/fnins.2014.00052. PMC 3957495. PMID 24672423.
  15. ↑ Hara Y, Ueta Y, Isse T, Kabashima N, Shibuya I, Hattori Y, Yamashita H (1997). "Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation". Neuroscience Letters. 229 (1): 65–8. doi:10.1016/S0304-3940(97)00419-9. PMID 9224803.
  16. ↑ Lim MM, Tsivkovskaia NO, Bai Y, Young LJ, Ryabinin AE (2006-01-01). "Distribution of corticotropin-releasing factor and urocortin 1 in the vole brain". Brain, Behavior and Evolution. 68 (4): 229–40. doi:10.1159/000094360. PMC 1828133. PMID 16816534.
  17. ↑ Kishimoto T, Pearse RV, Lin CR, Rosenfeld MG (February 1995). "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): 1108–12. doi:10.1073/pnas.92.4.1108. PMC 42647. PMID 7755719.
  18. ↑ Brar BK, Jonassen AK, Stephanou A, Santilli G, Railson J, Knight RA, Yellon DM, Latchman DS (March 2000). "Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway". The Journal of Biological Chemistry. 275 (12): 8508–14. doi:10.1074/jbc.275.12.8508. PMID 10722688.
  19. ↑ 19.0 19.1 Boorse GC, Crespi EJ, Dautzenberg FM, Denver RJ (November 2005). "Urocortins of the South African clawed frog, Xenopus laevis: conservation of structure and function in tetrapod evolution". Endocrinology. 146 (11): 4851–60. doi:10.1210/en.2005-0497. PMID 16037378.

Further reading

  • Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A, Meguid MM, Fujimiya M (March 2004). "Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endocrine organ". FASEB Journal. 18 (3): 439–56. doi:10.1096/fj.03-0641rev. PMID 15003990.
  • Huang Y, Yao XQ, Lau CW, Chan YC, Tsang SY, Chan FL (Mar 2004). "Urocortin and cardiovascular protection". Acta Pharmacol Sin. 25 (3): 257–65.
  • Takahashi, Kazuhiro (2004). "Translational medicine in fish-derived peptides: From fish endocrinology to human physiology and diseases". Endocrine Journal (Kyoto, Japan). 51 (1): 1–17. doi:10.1507/endocrj.51.1.
  • Adachi T, Schamel WW, Kim KM, Watanabe T, Becker B, Nielsen PJ, Reth M (April 1996). "The specificity of association of the IgD molecule with the accessory proteins BAP31/BAP29 lies in the IgD transmembrane sequence". The EMBO Journal. 15 (7): 1534–41. PMC 450061. PMID 8612576.
  • Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T (November 1997). "Urocortin expression in human pituitary gland and pituitary adenoma". The Journal of Clinical Endocrinology and Metabolism. 82 (11): 3842–50. doi:10.1210/jc.82.11.3842. PMID 9360550.
  • 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.
  • Bamberger CM, Wald M, Bamberger AM, Ergün S, Beil FU, Schulte HM (February 1998). "Human lymphocytes produce urocortin, but not corticotropin-releasing hormone". The Journal of Clinical Endocrinology and Metabolism. 83 (2): 708–11. doi:10.1210/jc.83.2.708. PMID 9467598.
  • Takahashi K, Totsune K, Sone M, Murakami O, Satoh F, Arihara Z, Sasano H, Iino K, Mouri T (1998). "Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain". Peptides. 19 (4): 643–7. doi:10.1016/S0196-9781(98)00012-6. PMID 9622018.
  • Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Takahashi K, Suzuki H, Tezuka F, Yoshimi T, Nagura H (January 1999). "Urocortin expression in the human central nervous system". Clinical Endocrinology. 50 (1): 107–14. doi:10.1046/j.1365-2265.1999.00624.x. PMID 10341863.
  • Watanabe F, Oki Y, Ozawa M, Masuzawa M, Iwabuchi M, Yoshimi T, Nishiguchi T, Iino K, Sasano H (1999). "Urocortin in human placenta and maternal plasma". Peptides. 20 (2): 205–9. doi:10.1016/S0196-9781(98)00175-2. PMID 10422876.
  • Slominski A, Roloff B, Curry J, Dahiya M, Szczesniewski A, Wortsman J (February 2000). "The skin produces urocortin". The Journal of Clinical Endocrinology and Metabolism. 85 (2): 815–23. doi:10.1210/jc.85.2.815. PMID 10690896.
  • Muramatsu Y, Fukushima K, Iino K, Totsune K, Takahashi K, Suzuki T, Hirasawa G, Takeyama J, Ito M, Nose M, Tashiro A, Hongo M, Oki Y, Nagura H, Sasano H (December 2000). "Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa". Peptides. 21 (12): 1799–809. doi:10.1016/S0196-9781(00)00335-1. PMID 11150640.
  • Muramatsu Y, Sugino N, Suzuki T, Totsune K, Takahashi K, Tashiro A, Hongo M, Oki Y, Sasano H (March 2001). "Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries". The Journal of Clinical Endocrinology and Metabolism. 86 (3): 1362–9. doi:10.1210/jc.86.3.1362. PMID 11238533.
  • Hsu SY, Hsueh AJ (May 2001). "Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor". Nature Medicine. 7 (5): 605–11. doi:10.1038/87936. PMID 11329063.
  • Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (June 2001). "Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor". Proceedings of the National Academy of Sciences of the United States of America. 98 (13): 7570–5. doi:10.1073/pnas.121165198. PMC 34709. PMID 11416224.
  • Kimura Y, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Darnel AD, Suzuki T, Ebina M, Nukiwa T, Sasano H (January 2002). "Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart". The Journal of Clinical Endocrinology and Metabolism. 87 (1): 340–6. doi:10.1210/jc.87.1.340. PMID 11788672.
  • Florio P, Arcuri F, Ciarmela P, Runci Y, Romagnoli R, Cintorino M, Di Blasio AM, Petraglia F (May 2002). "Identification of urocortin mRNA and peptide in the human endometrium". The Journal of Endocrinology. 173 (2): R9–14. doi:10.1677/joe.0.173R009. PMID 12010647.
  • Arcuri F, Cintorino M, Florio P, Floccari F, Pergola L, Romagnoli R, Petraglia F, Tosi P, Teresa Del Vecchio M (August 2002). "Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma". The Prostate. 52 (3): 167–72. doi:10.1002/pros.10094. PMID 12111693.
  • Ikeda K, Tojo K, Oki Y, Nakao K (September 2002). "Urocortin has cell-proliferative effects on cardiac non-myocytes". Life Sciences. 71 (16): 1929–38. doi:10.1016/S0024-3205(02)01945-8. PMID 12175707.
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