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Gene Review

UCN  -  urocortin

Homo sapiens

Synonyms: UI, UROC, Urocortin
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Disease relevance of UCN


Psychiatry related information on UCN


High impact information on UCN

  • UCN I was shown to directly alter the glucose sensitivity of VMH glucose-sensing neurons in whole-cell current clamp recordings in brain slices [8].
  • In this issue of the JCI, McCrimmon and colleagues report that application of urocortin I (a corticotrophin-releasing factor receptor-2 agonist) to the ventromedial hypothalamus reduces the glucose counterregulatory response to hypoglycemia in rats (see the related article beginning on page 1723) [9].
  • Thus, hypothalamic urocortin I release during antecedent hypoglycemia is, among other possibilities, a potential mechanism of HAAF [9].
  • Those displaying vasoactivity all function as directly acting vasodilators and include adrenomedullin and the emerging urocortin transmitters [10].
  • Corticotropin-releasing factor (CRF), its structurally related peptide urocortin (Ucn) and their receptors are also present in the skin and their levels are increased following stress [11].

Chemical compound and disease context of UCN


Biological context of UCN


Anatomical context of UCN

  • Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells [3].
  • UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta [3].
  • Immunoreactive UCN was found in luminal and glandular epithelial cells in healthy, but not in neoplastic samples [2].
  • This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin [3].
  • In cultured human pregnant myometrial cells, urocortin but not CRH was able to induce MAPK phosphorylation and activation, suggesting that in the human myometrium these two peptides have distinct actions and biological roles [18].

Associations of UCN with chemical compounds


Physical interactions of UCN

  • In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis [20].
  • Urocortin has been found to bind with high affinity to CRF receptors [21].

Enzymatic interactions of UCN

  • No UCN-01-induced G1 accumulation in SBC-3 cells was observed in SBC-3/UCN cells and decreased expression of phosphorylated RB protein was found in SBC-3 cells [22].

Regulatory relationships of UCN


Other interactions of UCN

  • Studies on Gq protein activation using [alpha-32P]-GTP-gamma-azidoanilide and IP3 production in cells expressing the R1alpha or R2beta CRH receptors demonstrated that urocortin was 10 times more potent than CRH [18].
  • Adipose tissue also expressed urocortin and stresscopin, the predominant ligands of peripheral CRH-R2 [25].
  • The inhibitory effect of the CRF-binding protein on human urocortin can be blocked by biologically inactive CRF fragments, such as CRF(9-33) [26].
  • Synthetic human urocortin binds with high affinity to CRF receptor types 1, 2 alpha, and 2 beta, stimulates cAMP accumulation from cells stably transfected with these receptors, and acts in vitro to release ACTH from dispersed rat anterior pituitary cells [26].
  • Urocortin in the synovial tissue of patients with rheumatoid arthritis [27].

Analytical, diagnostic and therapeutic context of UCN

  • Here we demonstrate the presence of UCN mRNA in both the rat spleen and human Jurkat T-lymphoma cells using 3'-RACE (rapid amplication of cDNA ends) PCR [28].
  • Immunohistochemistry was used to evaluate cellular UCN localization, with the intensity of immunostaining scored on a subjective scale [2].
  • We studied the concentration of urocortin in the synovial fluid using RIA, and the expression of urocortin in synovial tissue using immunohistochemistry, mRNA in situ hybridization and reverse transcriptase-PCR (RT-PCR) [27].
  • Interestingly, the suppressive effect of UCN I-mediated CRFR2 activation persisted for at least 24 hours after in vivo VMH microinjection [8].
  • Reverse phase high-performance liquid chromatography of the UCN-LI in the human brain extract showed two immunoreactive peaks; one peak eluting earlier and one in the position of synthetic human UCN [29].


  1. Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes. Chanalaris, A., Lawrence, K.M., Stephanou, A., Knight, R.D., Hsu, S.Y., Hsueh, A.J., Latchman, D.S. J. Mol. Cell. Cardiol. (2003) [Pubmed]
  2. Urocortin expression is downregulated in human endometrial carcinoma. Florio, P., De Falco, G., Leucci, E., Torricelli, M., Torres, P.B., Toti, P., Dell'Anna, A., Tiso, E., Santopietro, R., Leoncini, L., Petraglia, F. J. Endocrinol. (2006) [Pubmed]
  3. Expression of urocortin in the extravillous human trophoblast at the implantation site. Bamberger, C.M., Minas, V., Bamberger, A.M., Charalampopoulos, I., Fragouli, Y., Schulte, H.M., Makrigiannakis, A. Placenta (2007) [Pubmed]
  4. Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. Kimura, Y., Takahashi, K., Totsune, K., Muramatsu, Y., Kaneko, C., Darnel, A.D., Suzuki, T., Ebina, M., Nukiwa, T., Sasano, H. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  5. Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa. 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. Peptides (2000) [Pubmed]
  6. Injections of urocortin 1 into the basolateral amygdala induce anxiety-like behavior and c-Fos expression in brainstem serotonergic neurons. Spiga, F., Lightman, S.L., Shekhar, A., Lowry, C.A. Neuroscience (2006) [Pubmed]
  7. 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]
  8. Corticotrophin-releasing factor receptors within the ventromedial hypothalamus regulate hypoglycemia-induced hormonal counterregulation. McCrimmon, R.J., Song, Z., Cheng, H., McNay, E.C., Weikart-Yeckel, C., Fan, X., Routh, V.H., Sherwin, R.S. J. Clin. Invest. (2006) [Pubmed]
  9. Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes. Cryer, P.E. J. Clin. Invest. (2006) [Pubmed]
  10. Regulation of vascular reactivity by established and emerging GPCRs. Maguire, J.J., Davenport, A.P. Trends Pharmacol. Sci. (2005) [Pubmed]
  11. Mast cells as targets of corticotropin-releasing factor and related peptides. Theoharides, T.C., Donelan, J.M., Papadopoulou, N., Cao, J., Kempuraj, D., Conti, P. Trends Pharmacol. Sci. (2004) [Pubmed]
  12. Peripheral urocortin delays gastric emptying: role of CRF receptor 2. Nozu, T., Martinez, V., Rivier, J., Taché, Y. Am. J. Physiol. (1999) [Pubmed]
  13. Expression of urocortin in rat lung and its effect on pulmonary vascular permeability. Wu, Y., Xu, Y., Zhou, H., Tao, J., Li, S. J. Endocrinol. (2006) [Pubmed]
  14. The action of urocortins on body temperature in rats. Telegdy, G., Adamik, A., Tóth, G. Peptides (2006) [Pubmed]
  15. High levels of intrauterine corticotrophin-releasing hormone, urocortin, tryptase, and interleukin-8 in spontaneous abortions. Florio, P., Ciarmela, P., Arcuri, F., Petraglia, F. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  16. Identification of Signaling Molecules Mediating Corticotropin-Releasing Hormone-R1{alpha}-Mitogen-Activated Protein Kinase (MAPK) Interactions: The Critical Role of Phosphatidylinositol 3-Kinase in Regulating ERK1/2 But Not p38 MAPK Activation. Punn, A., Levine, M.A., Grammatopoulos, D.K. Mol. Endocrinol. (2006) [Pubmed]
  17. Differential regulation of CREB and ERK phosphorylation through corticotropin-releasing factor receptors type 1 and 2 in AtT-20 and A7r5 cells. Kageyama, K., Hanada, K., Moriyama, T., Imaizumi, T., Satoh, K., Suda, T. Mol. Cell. Endocrinol. (2007) [Pubmed]
  18. Urocortin, but not corticotropin-releasing hormone (CRH), activates the mitogen-activated protein kinase signal transduction pathway in human pregnant myometrium: an effect mediated via R1alpha and R2beta CRH receptor subtypes and stimulation of Gq-proteins. Grammatopoulos, D.K., Randeva, H.S., Levine, M.A., Katsanou, E.S., Hillhouse, E.W. Mol. Endocrinol. (2000) [Pubmed]
  19. Placental corticotropin-releasing factor. An update. Fadalti, M., Pezzani, I., Cobellis, L., Springolo, F., Petrovec, M.M., Ambrosini, G., Reis, F.M., Petraglia, F. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  20. Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner. Dermitzaki, E., Tsatsanis, C., Minas, V., Chatzaki, E., Charalampopoulos, I., Venihaki, M., Androulidaki, A., Lambropoulou, M., Spiess, J., Michalodimitrakis, E., Gravanis, A., Margioris, A.N. Endocrinology (2007) [Pubmed]
  21. Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries. Muramatsu, Y., Sugino, N., Suzuki, T., Totsune, K., Takahashi, K., Tashiro, A., Hongo, M., Oki, Y., Sasano, H. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  22. Molecular determinants of UCN-01-induced growth inhibition in human lung cancer cells. Usuda, J., Saijo, N., Fukuoka, K., Fukumoto, H., Kuh, H.J., Nakamura, T., Koh, Y., Suzuki, T., Koizumi, F., Tamura, T., Kato, H., Nishio, K. Int. J. Cancer (2000) [Pubmed]
  23. Human CRF2 alpha and beta splice variants: pharmacological characterization using radioligand binding and a luciferase gene expression assay. Ardati, A., Goetschy, V., Gottowick, J., Henriot, S., Valdenaire, O., Deuschle, U., Kilpatrick, G.J. Neuropharmacology (1999) [Pubmed]
  24. Levels of maternal plasma corticotropin-releasing factor and urocortin during labor. Florio, P., Cobellis, L., Woodman, J., Severi, F.M., Linton, E.A., Petraglia, F. J. Soc. Gynecol. Investig. (2002) [Pubmed]
  25. Corticotropin-releasing hormone system in human adipose tissue. Seres, J., Bornstein, S.R., Seres, P., Willenberg, H.S., Schulte, K.M., Scherbaum, W.A., Ehrhart-Bornstein, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  26. Cloning and characterization of human urocortin. Donaldson, C.J., Sutton, S.W., Perrin, M.H., Corrigan, A.Z., Lewis, K.A., Rivier, J.E., Vaughan, J.M., Vale, W.W. Endocrinology (1996) [Pubmed]
  27. Urocortin in the synovial tissue of patients with rheumatoid arthritis. Uzuki, M., Sasano, H., Muramatsu, Y., Totsune, K., Takahashi, K., Oki, Y., Iino, K., Sawai, T. Clin. Sci. (2001) [Pubmed]
  28. mRNA expression profiles for corticotrophin-releasing factor (CRF), urocortin, CRF receptors and CRF-binding protein in peripheral rat tissues. Baigent, S.M., Lowry, P.J. J. Mol. Endocrinol. (2000) [Pubmed]
  29. Regional distribution of urocortin-like immunoreactivity and expression of urocortin mRNA in the human brain. Takahashi, K., Totsune, K., Sone, M., Murakami, O., Satoh, F., Arihara, Z., Sasano, H., Iino, K., Mouri, T. Peptides (1998) [Pubmed]
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