Cellular and Molecular Life Sciences

, Volume 67, Issue 8, pp 1293–1306 | Cite as

The corticotropin releasing factor system in cancer: expression and pathophysiological implications

  • Athina Kaprara
  • Kalliopi Pazaitou-Panayiotou
  • Alexandros Kortsaris
  • Ekaterini Chatzaki
Review
First Online:
Received:
Revised:
Accepted:

Abstract

Malignant tumors express multiple factors that have some role in the regulating networks supporting their ectopic growth. Recently, increased interest has been developing in the expression and biological role of the neuropeptides and receptors of the corticotropin releasing factor (CRF) system, the principal neuroendocrine mediator of the stress response, especially in the light of several R&D programs for small molecule antagonists that could present some anticancer therapeutic benefit. In the present article, we review the literature suggesting that the CRF system could be involved in the regulation of human cancer development. Potential implication in growth, metastasis, angiogenesis, or immune parameters via activation of locally expressed receptors could be clinically exploited by presenting targets of new therapeutic approaches.

Keywords

Corticotropin releasing factor Urocortin Receptor Human Cancer 
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References

  1. 1.
    Spiess J, Rivier J, Rivier C, Vale W (1981) Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc Natl Acad Sci USA 78:6517–6521PubMedGoogle Scholar
  2. 2.
    Pohl S, Darlison MG, Clarke WC, Lederis K, Richter D (2001) Cloning and functional pharmacology of two corticotropin-releasing factor receptors from a teleost fish. Eur J Pharmacol 430:193–202PubMedGoogle Scholar
  3. 3.
    Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (1996) Cloning and characterization of human urocortin published erratum appears in endocrinology 1996 Sep; 137(9):3896. Endocrinology 137:2167–70Google Scholar
  4. 4.
    Guillemin R, Rosenberg B (1955) Humoral hypothalamic control of anterior pituitary: a study with combined tissue cultures. Endocrinology 57:599–607PubMedGoogle Scholar
  5. 5.
    Saffran M, Schally AV (1955) The release of corticotrophin by anterior pituitary tissue in vitro. Can J Biochem Physiol 33:408–415PubMedGoogle Scholar
  6. 6.
    Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397PubMedGoogle Scholar
  7. 7.
    Takahashi K, Hara E, Suzuki H, Sasano H, Shibahara S (1996) Expression of heme oxygenase isozyme mRNAs in the human brain and induction of heme oxygenase-1 by nitric oxide donors. J Neurochem 67:482–489PubMedGoogle Scholar
  8. 8.
    Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor see comments. Nature 378:287–292PubMedGoogle Scholar
  9. 9.
    Hsu SY, Hsueh AJ (2001) Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nat Med 7:605–611PubMedGoogle Scholar
  10. 10.
    Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenesch JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE (2001) Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors. Proc Natl Acad Sci USA 98:2843–2848PubMedGoogle Scholar
  11. 11.
    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 (2001) Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc Natl Acad Sci USA 98:7570–7575PubMedGoogle Scholar
  12. 12.
    Iino K, Sasano H, Oki Y, Andoh N, Shin RW, Kitamoto T, Totsune K, Takahashi K, Suzuki H, Nagura H, Yoshimi T (1997) Urocortin expression in human pituitary gland and pituitary adenoma. J Clin Endocrinol Metab 82:3842–3850PubMedGoogle Scholar
  13. 13.
    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 19:643–647PubMedGoogle Scholar
  14. 14.
    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 (2000) Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa. Peptides 21:1799–1809PubMedGoogle Scholar
  15. 15.
    Muramatsu Y, Sugino N, Suzuki T, Totsune K, Takahashi K, Tashiro A, Hongo M, Oki Y, Sasano H (2001) Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries. J Clin Endocrinol Metab 86:1362–1369PubMedGoogle Scholar
  16. 16.
    Kimura Y, Takahashi K, Totsune K, Muramatsu Y, Kaneko C, Darnel AD, Suzuki T, Ebina M, Nukiwa T, Sasano H (2002) Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart. J Clin Endocrinol Metab 87:340–346PubMedGoogle Scholar
  17. 17.
    Takahashi K, Totsune K, Murakami O, Saruta M, Nakabayashi M, Suzuki T, Sasano H, Shibahara S (2004) Expression of urocortin III/stresscopin in human heart and kidney. J Clin Endocrinol Metab 89:1897–1903PubMedGoogle Scholar
  18. 18.
    Saruta M, Takahashi K, Suzuki T, Fukuda T, Torii A, Sasano H (2005) Urocortin 3/stresscopin in human colon: possible modulators of gastrointestinal function during stressful conditions. Peptides 26:1196–1206PubMedGoogle Scholar
  19. 19.
    Florio P, Torres PB, Torricelli M, Toti P, Vale W, Petraglia F (2006) Human endometrium expresses urocortin II and III messenger RNA and peptides. Fertil Steril 86:1766–1770PubMedGoogle Scholar
  20. 20.
    Kageyama K, Bradbury MJ, Zhao L, Blount AL, Vale WW (1999) Urocortin messenger ribonucleic acid: tissue distribution in the rat and regulation in thymus by lipopolysaccharide and glucocorticoids. Endocrinology 140:5651–5658PubMedGoogle Scholar
  21. 21.
    Suda T, Kageyama K, Sakihara S, Nigawara T (2004) Physiological roles of urocortins, human homologues of fish urotensin I, and their receptors. Peptides 25:1689–1701PubMedGoogle Scholar
  22. 22.
    Kishimoto T, Radulovic J, Radulovic M, Lin CR, Schrick C, Hooshmand F, Hermanson O, Rosenfeld MG, Spiess J (2000) Deletion of crhr2 reveals an anxiolytic role for corticotropin- releasing hormone receptor-2. Nat Genet 24:415–419PubMedGoogle Scholar
  23. 23.
    Vale WW, Vaughn J, Perrin M (1997) Corticotropin-releasing factor (CRF) family of ligands and their receptors. Endocrinologist 7:3S–9SGoogle Scholar
  24. 24.
    Jahn O, Radulovic J, Stiedl O, Tezval H, Eckart K, Spiess J (2005) Corticotropin-releasing factor binding protein–a ligand trap? Mini Rev Med Chem 5:953–960PubMedGoogle Scholar
  25. 25.
    Asa SL, Kovacs K, Vale W, Petrusz P, Vecsei P (1987) Immunohistologic localization of corticotrophin-releasing hormone in human tumors. Am J Clin Pathol 87:327–333PubMedGoogle Scholar
  26. 26.
    Fjellestad-Paulsen A, Abrahamsson PA, Bjartell A, Grino M, Grimelius L, Hedeland H, Falkmer S (1988) Carcinoma of the prostate with Cushing’s syndrome. A case report with histochemical and chemical demonstration of immunoreactive corticotropin-releasing hormone in plasma and tumoral tissue. Acta Endocrinol (Copenhagen) 119:506–516Google Scholar
  27. 27.
    Yamada Y, Ohashi A, Inoue T, Sakaguchi K, Tsujimura T, Okamoto D, Itatani H, Fujimoto N, Kusaka K, Fushimi H (2002) Cushing’s syndrome with a large pituitary adenoma producing both corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH). Int Med 41:549–554Google Scholar
  28. 28.
    Arcuri F, Cintorino M, Florio P, Floccari F, Pergola L, Romagnoli R, Petraglia F, Tosi P, Teresa Del Vecchio M (2002) Expression of urocortin mRNA and peptide in the human prostate and in prostatic adenocarcinoma. Prostate 52:167–172PubMedGoogle Scholar
  29. 29.
    Reubi JC, Waser B, Vale W, Rivier J (2003) Expression of CRF1 and CRF2 receptors in human cancers. J Clin Endocrinol Metab 88:3312–3320PubMedGoogle Scholar
  30. 30.
    Tezval H, Jurk S, Atschekzei F, Serth J, Kuczyk MA, Merseburger AS (2009) The involvement of altered corticotropin releasing factor receptor 2 expression in prostate cancer due to alteration of anti-angiogenic signaling pathways. Prostate 69:443–448PubMedGoogle Scholar
  31. 31.
    Makrigiannakis A, Zoumakis E, Margioris AN, Theodoropoulos P, Stournaras C, Gravanis A (1995) The corticotropin-releasing hormone (CRH) in normal and tumoral epithelial cells of human endometrium. J Clin Endocrinol Metab 80:185–189PubMedGoogle Scholar
  32. 32.
    Graziani G, Tentori L, Portarena I, Barbarino M, Tringali G, Pozzoli G, Navarra P (2002) CRH inhibits cell growth of human endometrial adenocarcinoma cells via CRH-receptor 1-mediated activation of cAMP-PKA pathway. Endocrinology 143:807–813PubMedGoogle Scholar
  33. 33.
    Graziani G, Ferrandina G, Pozzoli G, Vergati M, Muzi A, Legge F, Tentori L, Scambia G, Navarra P (2006) Corticotropin-releasing hormone receptor-1 in human endometrial cancer. Oncol Rep 15:375–379PubMedGoogle Scholar
  34. 34.
    Florio P, De Falco G, Leucci E, Torricelli M, Torres PB, Toti P, Dell’Anna A, Tiso E, Santopietro R, Leoncini L, Petraglia F (2006) Urocortin expression is downregulated in human endometrial carcinoma. J Endocrinol 190:99–105PubMedGoogle Scholar
  35. 35.
    Miceli F, Ranelletti FO, Martinelli E, Petrillo M, Scambia G, Navarra P, Ferrandina G (2009) Expression and subcellular localization of CRH and its receptors in human endometrial cancer. Mol Cell Endocrinol 305:6–11PubMedGoogle Scholar
  36. 36.
    Ciocca DR, Puy LA, Fasoli LC, Tello O, Aznar JC, Gago FE, Papa SI, Sonego R (1990) Corticotropin-releasing hormone, luteinizing hormone-releasing hormone, growth hormone-releasing hormone, and somatostatin-like immunoreactivities in biopsies from breast cancer patients. Breast Cancer Res Treat 15:175–184PubMedGoogle Scholar
  37. 37.
    Tjuvajev J, Kolesnikov Y, Joshi R, Sherinski J, Koutcher L, Zhou Y, Matei C, Koutcher J, Kreek MJ, Blasberg R (1998) Anti-neoplastic properties of human corticotropin releasing factor: involvement of the nitric oxide pathway. In Vivo 12:1–10PubMedGoogle Scholar
  38. 38.
    Parham KL, Zervou S, Karteris E, Catalano RD, Old RW, Hillhouse EW (2004) Promoter analysis of human corticotropin-releasing factor (CRF) type 1 receptor and regulation by CRF and urocortin. Endocrinology 145:3971–3983PubMedGoogle Scholar
  39. 39.
    Graziani G, Tentori L, Muzi A, Vergati M, Tringali G, Pozzoli G, Navarra P (2007) Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype. Mol Cell Endocrinol 264:44–49PubMedGoogle Scholar
  40. 40.
    Androulidaki A, Dermitzaki E, Venihaki M, Karagianni E, Rassouli O, Andreakou E, Stournaras C, Margioris AN, Tsatsanis C (2009) Corticotropin releasing factor promotes breast cancer cell motility and invasiveness. Mol Cancer 8:30PubMedGoogle Scholar
  41. 41.
    Suda T, Tomori N, Yajima F, Odagiri E, Demura H, Shizume K (1986) Characterization of immunoreactive corticotropin and corticotropin: releasing factor in human adrenal and ovarian tumours. Acta Endocrinol (Copenhagen) 111:546–552Google Scholar
  42. 42.
    Zoumakis E, Chatzaki E, Charalampopoulos I, Margioris AN, Angelakis E, Koumantakis E, Gravanis A (2001) Cycle and age-related changes in corticotropin-releasing hormone levels in human endometrium and ovaries. Gynecol Endocrinol 15:98–102PubMedGoogle Scholar
  43. 43.
    Minas V, Rolaki A, Kalantaridou SN, Sidiropoulos J, Mitrou S, Petsas G, Jeschke U, Paraskevaidis EA, Fountzilas G, Chrousos GP, Pavlidis N, Makrigiannakis A (2007) Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation. Br J Cancer 97:637–645PubMedGoogle Scholar
  44. 44.
    De Groef B, Van der Geyten S, Darras VM, Kuhn ER (2006) Role of corticotropin-releasing hormone as a thyrotropin-releasing factor in non-mammalian vertebrates. Gen Comp Endocrinol 146:62–68PubMedGoogle Scholar
  45. 45.
    Birkenhager JC, Upton GV, Seldenrath HJ, Krieger DT, Tashjian AH Jr (1976) Medullary thyroid carcinoma: ectopic production of peptides with ACTH- like, corticotrophin releasing factor-like and prolactin production- stimulating activities. Acta Endocrinol (Copenhagen) 83:280–292Google Scholar
  46. 46.
    Wakabayashi I, Ihara T, Hattori M, Tonegawa Y, Shibasaki T, Hashimoto K (1985) Presence of corticotropin-releasing factor-like immunoreactivity in human tumors. Cancer 55:995–1000PubMedGoogle Scholar
  47. 47.
    Delgrange E, Maiter D, Donckier J, Tourniaire J (1999) Influence of age on the clinical presentation of prolactinomas in male patients. Gerontology 45:160–164PubMedGoogle Scholar
  48. 48.
    Scopa CD, Mastorakos G, Friedman TC, Melachrinou M, Merino MJ, Chrousos GP (1994) Presence of immunoreactive corticotropin releasing hormone in thyroid lesions. Am J Pathol 145:1159–1167PubMedGoogle Scholar
  49. 49.
    Tagliabue M, Pagani A, Palestini N, Manieri C, Martina V (1996) Multiple endocrine neoplasia (MEN IIB) with Cushing’s syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone. Panminerva Med 38:41–44PubMedGoogle Scholar
  50. 50.
    Chrisoulidou A, Pazaitou-Panayiotou K, Georgiou E, Boudina M, Kontogeorgos G, Iakovou I, Efstratiou I, Patakiouta F, Vainas I (2008) Ectopic Cushing’s syndrome due to CRH secreting liver metastasis in a patient with medullary thyroid carcinoma. Hormones (Athens) 7:259–262Google Scholar
  51. 51.
    Kageyama K, Sakihara S, Yamashita M, Takahashi K, Kawashima S, Tanabe J, Tsutaya S, Yasujima M, Suda T (2008) A case of multiple endocrine neoplasia type II accompanied by thyroid medullary carcinoma and pheochromocytomas expressing corticotropin-releasing factor and urocortins. Am J Med Sci 335:398–402PubMedGoogle Scholar
  52. 52.
    Slominski A, Zbytek B, Zmijewski M, Slominski RM, Kauser S, Wortsman J, Tobin DJ (2006) Corticotropin releasing hormone and the skin. Front Biosci 11:2230–2248PubMedGoogle Scholar
  53. 53.
    Slominski A, Ermak G, Mazurkiewicz JE, Baker J, Wortsman J (1998) Characterization of corticotropin-releasing hormone (CRH) in human skin. J Clin Endocrinol Metab 83:1020–1024PubMedGoogle Scholar
  54. 54.
    Fazal N, Slominski A, Choudhry MA, Wei ET, Sayeed MM (1998) Effect of CRF and related peptides on calcium signaling in human and rodent melanoma cells. FEBS Lett 435:187–190PubMedGoogle Scholar
  55. 55.
    Funasaka Y, Sato H, Ichihashi M (1999) Expression of corticotropin releasing hormone in malignant melanoma. Ann N Y Acad Sci 885:391–393PubMedCrossRefGoogle Scholar
  56. 56.
    Sato H, Nagashima Y, Chrousos GP, Ichihashi M, Funasak Y (2002) The expression of corticotropin-releasing hormone in melanoma. Pigment Cell Res 15:98–103PubMedGoogle Scholar
  57. 57.
    Kim MH, Cho D, Kim HJ, Chong SJ, Lee KH, Yu DS, Park CJ, Lee JY, Cho BK, Park HJ (2006) Investigation of the corticotropin-releasing hormone-proopiomelanocortin axis in various skin tumours. Br J Dermatol 155:910–915PubMedGoogle Scholar
  58. 58.
    Yang Y, Park H, Yang Y, Kim TS, Bang SI, Cho D (2007) Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2 pathway in murine melanoma cell line, B16F10. Exp Dermatol 16:22–27PubMedGoogle Scholar
  59. 59.
    Carlson KW, Nawy SS, Wei ET, Sadee W, Filov VA, Rezsova VV, Slominski A, Quillan JM (2001) Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs. Anticancer Res 21:1173–1179PubMedGoogle Scholar
  60. 60.
    Tsuchihashi T, Yamaguchi K, Abe K, Yanaihara N, Saito S (1992) Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors. Jpn J Clin Oncol 22:232–237PubMedGoogle Scholar
  61. 61.
    Bahro M, Pfeifer U, Dammrich J (1992) Involvement of autophagic degradation in ACTH-induced skeletal muscle atrophy. Clin Neuropathol 11:64–70PubMedGoogle Scholar
  62. 62.
    Auchus RJ, Mastorakos G, Friedman TC, Chrousos GP (1994) Corticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing’s syndrome. J Endocrinol Invest 17:447–452PubMedGoogle Scholar
  63. 63.
    Suda T, Tozawa F, Dobashi I, Horiba N, Ohmori N, Yamakado M, Yamada M, Demura H (1993) Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin- producing tumors in vitro. J Clin Invest 92:2790–2795PubMedGoogle Scholar
  64. 64.
    Calogero AE, Polosa R, Neville E, D’Agata R (1995) Measurements of hormonal peptides in the bronchoalveolar fluid as tumor markers of lung cancer. J Endocrinol Invest 18:354–358PubMedGoogle Scholar
  65. 65.
    Calogero AE, Minacapilli G, Nicolosi AM, Moncada ML, Mistretta A, Latteri SF, Polosa P, D’Agata R (1992) Limited clinical usefulness of plasma corticotropin-releasing hormone, adrenocorticotropin and beta-endorphin measurements as markers of lung cancer. J Endocrinol Invest 15:581–586PubMedGoogle Scholar
  66. 66.
    Dieterich KD, Lehnert H (2000) Decreased expression of corticotropin-releasing factor-binding protein mRNA in ACTH-secreting pituitary adenomas. Exp Clin Endocrinol Diabetes 108:59–62PubMedGoogle Scholar
  67. 67.
    Moody TW, Zia F, Venugopal R, Korman LY, Goldstein AL, Fagarasan M (1994) Corticotropin-releasing factor stimulates cyclic AMP, arachidonic acid release, and growth of lung cancer cells. Peptides 15:281–285PubMedGoogle Scholar
  68. 68.
    Argiles JM, Figueras M, Ametller E, Fuster G, Olivan M, de Oliveira CC, Lopez-Soriano FJ, Isfort RJ, Busquets S (2008) Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells. Muscle Nerve 37:190–195PubMedGoogle Scholar
  69. 69.
    Paschos KA, Charsou C, Constantinidis TC, Anagnostoulis S, Lambropoulou M, Papachristou F, Simopoulos K, Chatzaki E (2010) Corticotropin releasing hormone receptors mediate opposing effects in cholestasis-induced liver cell apoptosis. Endocrinology (in press)Google Scholar
  70. 70.
    Park SY, Rhee Y, Youn JC, Park YN, Lee S, Kim DM, Song SY, Lim SK (2007) Ectopic Cushing’s syndrome due to concurrent corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) secreted by malignant gastrinoma. Exp Clin Endocrinol Diabetes 115:13–16PubMedGoogle Scholar
  71. 71.
    Simopoulos C, Christodoulou E, Lambropoulou M, Tsaroucha AK, Kakolyris S, Polychronidis A, Karayiannakis AJ, Chatzaki E (2009) Neuropeptide urocortin 1 and its receptors expressed human liver. Neuroendocrinology 89:315–326Google Scholar
  72. 72.
    Wang J, Xu Y, Xu Y, Zhu H, Zhang R, Zhang G, Li S (2008) Urocortin’s inhibition of tumor growth and angiogenesis in hepatocellular carcinoma via corticotrophin-releasing factor receptor 2. Cancer Invest 26:359–368PubMedGoogle Scholar
  73. 73.
    Chatzaki E, Crowe PD, Wang L, Million M, Tache Y, Grigoriadis DE (2004) CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon. J Neurochem 90:309–316PubMedGoogle Scholar
  74. 74.
    Kohno M, Kawahito Y, Tsubouchi Y, Hashiramoto A, Yamada R, Inoue KI, Kusaka Y, Kubo T, Elenkov IJ, Chrousos GP, Kondo M, Sano H (2001) Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: relation to inflammatory activity. J Clin Endocrinol Metab 86:4344–4352PubMedGoogle Scholar
  75. 75.
    Kozicz T, Arimura A (2002) Distribution of urocortin in the rat’s gastrointestinal tract and its colocalization with tyrosine hydroxylase. Peptides 23:515–521PubMedGoogle Scholar
  76. 76.
    Chatzaki E, Charalampopoulos I, Leontidis C, Mouzas IA, Tzardi M, Tsatsanis C, Margioris AN, Gravanis A (2003) Urocortin in human gastric mucosa: relationship to inflammatory activity. J Clin Endocrinol Metab 88:478–483PubMedGoogle Scholar
  77. 77.
    Chatzaki E, Murphy BJ, Wang L, Million M, Ohning GV, Crowe PD, Petroski R, Tache Y, Grigoriadis DE (2004) Differential profile of CRF receptor distribution in the rat stomach and duodenum assessed by newly developed CRF receptor antibodies. J Neurochem 88:1–11PubMedCrossRefGoogle Scholar
  78. 78.
    Chatzaki E, Lambropoulou M, Constantinidis TC, Papadopoulos N, Tache Y, Minopoulos G, Grigoriadis DE (2006) Corticotropin-releasing factor (CRF) receptor type 2 in the human stomach: Protective biological role by inhibition of apoptosis. J Cell Physiol 209:905–911PubMedGoogle Scholar
  79. 79.
    Lezoualc’h F, Engert S, Berning B, Behl C (2000) Corticotropin-releasing hormone-mediated neuroprotection against oxidative stress is associated with the increased release of non- amyloidogenic amyloid beta precursor protein and with the suppression of nuclear factor-kappaB. Mol Endocrinol 14:147–159PubMedGoogle Scholar
  80. 80.
    Karalis KP, Venihaki M, Zhao J, van Vlerken LE, Chandras C (2004) NF-kappaB participates in the corticotropin-releasing, hormone-induced regulation of the pituitary proopiomelanocortin gene. J Biol Chem 279:10837–10840PubMedGoogle Scholar
  81. 81.
    Smith EM, Gregg M, Hashemi F, Schott L, Hughes TK (2006) Corticotropin Releasing Factor (CRF) activation of NF-kappaB-directed transcription in leukocytes. Cell Mol Neurobiol 26:1021–1036PubMedGoogle Scholar
  82. 82.
    Zhao J, Karalis KP (2002) Regulation of nuclear factor-kappaB by corticotropin-releasing hormone in mouse thymocytes. Mol Endocrinol 16:2561–2570PubMedGoogle Scholar
  83. 83.
    Huang M, Kempuraj D, Papadopoulou N, Kourelis T, Donelan J, Manola A, Theoharides TC (2009) Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kappa B activation. J Mol Endocrinol 42:397–405PubMedGoogle Scholar
  84. 84.
    Yao M, Denver RJ (2007) Regulation of vertebrate corticotropin-releasing factor genes. Gen Comp Endocrinol 153:200–216PubMedGoogle Scholar
  85. 85.
    Vamvakopoulos NC, Sioutopoulou TO (1994) Human corticotropin-releasing hormone receptor gene (CRHR) is located on the long arm of chromosome 17 (17q12-qter). Chromosome Res 2:471–473PubMedGoogle Scholar
  86. 86.
    Rossant CJ, Pinnock RD, Hughes J, Hall MD, McNulty S (1999) 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. Endocrinology 140:1525–1536PubMedGoogle Scholar
  87. 87.
    Papadopoulou N, Chen J, Randeva HS, Levine MA, Hillhouse EW, Grammatopoulos DK (2004) Protein kinase A-induced negative regulation of the corticotropin-releasing hormone R1alpha receptor-extracellularly regulated kinase signal transduction pathway: the critical role of Ser301 for signaling switch and selectivity. Mol Endocrinol 18:624–639PubMedGoogle Scholar
  88. 88.
    Brar BK, Railson J, Stephanou A, Knight RA, Latchman DS (2002) Urocortin increases the expression of heat shock protein 90 in rat cardiac myocytes in a MEK1/2-dependent manner. J Endocrinol 172:283–293PubMedGoogle Scholar
  89. 89.
    Brar BK, Jonassen AK, Stephanou A, Santilli G, Railson J, Knight RA, Yellon DM, Latchman DS (2000) Urocortin protects against ischemic and reperfusion injury via a MAPK-dependent pathway. J Biol Chem 275:8508–8514PubMedGoogle Scholar
  90. 90.
    Chanalaris A, Lawrence KM, Stephanou A, Knight RD, Hsu SY, Hsueh AJ, Latchman DS (2003) Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes. J Mol Cell Cardiol 35:1295–1305PubMedGoogle Scholar
  91. 91.
    Punn A, Levine MA, Grammatopoulos DK (2006) Identification of signaling molecules mediating corticotropin-releasing hormone-R1alpha-mitogen-activated protein kinase (MAPK) interactions: the critical role of phosphatidylinositol 3-kinase in regulating ERK1/2 but not p38 MAPK activation. Mol Endocrinol 20:3179–3195PubMedGoogle Scholar
  92. 92.
    Chandras C, Koutmani Y, Kokkotou E, Pothoulakis C, Karalis KP (2009) Activation of phosphatidylinositol 3-kinase/protein kinase B by corticotropin-releasing factor in human monocytes. Endocrinology 150:4606–4614PubMedGoogle Scholar
  93. 93.
    Olianas MC, Lampis G, Onali P (1992) Human Y-79 retinoblastoma cells express functional corticotropin- releasing hormone receptors. Brain Res 593:304–306PubMedGoogle Scholar
  94. 94.
    Olianas MC, Lampis G, Onali P (1995) Human Y-79 retinoblastoma cells exhibit specific corticotropin-releasing hormone binding sites. J Neurochem 64:402–407PubMedCrossRefGoogle Scholar
  95. 95.
    Hauger RL, Dautzenberg FM, Flaccus A, Liepold T, Spiess J (1997) Regulation of corticotropin-releasing factor receptor function in human Y-79 retinoblastoma cells: rapid and reversible homologous desensitization but prolonged recovery. J Neurochem 68:2308–2316PubMedCrossRefGoogle Scholar
  96. 96.
    Gutknecht E, Hauger RL, Van der Linden I, Vauquelin G, Dautzenberg FM (2008) Expression, binding, and signaling properties of CRF2(a) receptors endogenously expressed in human retinoblastoma Y79 cells: passage-dependent regulation of functional receptors. J Neurochem 104:926–936PubMedGoogle Scholar
  97. 97.
    Gutknecht E, Van der Linden I, Van Kolen K, Verhoeven KF, Vauquelin G, Dautzenberg FM (2009) Molecular mechanisms of corticotropin-releasing factor receptor-induced calcium signaling. Mol Pharmacol 75:648–657PubMedGoogle Scholar
  98. 98.
    Dautzenberg FM, Hauger RL (2001) G-protein-coupled receptor kinase 3- and protein kinase C-mediated desensitization of the PACAP receptor type 1 in human Y-79 retinoblastoma cells. Neuropharmacology 40:394–407PubMedGoogle Scholar
  99. 99.
    Radulovic M, Hippel C, Spiess J (2003) Corticotropin-releasing factor (CRF) rapidly suppresses apoptosis by acting upstream of the activation of caspases. J Neurochem 84:1074–1085PubMedGoogle Scholar
  100. 100.
    Post A, Ohl F, Almeida OF, Binder EB, Rucker M, Welt S, Binder E, Holsboer F, Sillaber I (2005) Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919). Psychopharmacology (Berl) 180:150–158Google Scholar
  101. 101.
    Halasz I, Rittenhouse PA, Zorrilla EP, Redei E (1997) Sexually dimorphic effects of maternal adrenalectomy on hypothalamic corticotrophin-releasing factor, glucocorticoid receptor and anterior pituitary POMC mRNA levels in rat neonates. Brain Res Dev Brain Res 100:198–204PubMedGoogle Scholar
  102. 102.
    Chatzaki E, Minas V, Zoumakis E, Makrigiannakis A (2006) CRF receptor antagonists: utility in research and clinical practice. Curr Med Chem 13:2751–2760PubMedGoogle Scholar
  103. 103.
    Heinrichs SC, De Souza EB, Schulteis G, Lapsansky JL, Grigoriadis DE (2002) Brain penetrance, receptor occupancy and antistress in vivo efficacy of a small molecule corticotropin releasing factor type I receptor selective antagonist. Neuropsychopharmacology 27:194–202PubMedGoogle Scholar
  104. 104.
    Davis ME, Pemberton CJ, Yandle TG, Fisher SF, Lainchbury JG, Frampton CM, Rademaker MT, Richards M (2007) Urocortin 2 infusion in human heart failure. Eur Heart J 28:2589–2597PubMedGoogle Scholar
  105. 105.
    Davis ME, Pemberton CJ, Yandle TG, Lainchbury JG, Rademaker MT, Nicholls MG, Frampton CM, Richards AM (2005) Effect of urocortin 1 infusion in humans with stable congestive cardiac failure. Clin Sci (Lond) 109:381–388Google Scholar
  106. 106.
    Wang J, Li S (2007) Corticotropin-releasing factor family and its receptors: tumor therapeutic targets? Biochem Biophys Res Commun 362:785–788PubMedGoogle Scholar
  107. 107.
    Nishi Y, Takayanagi R, Yanase T, Haji M, Hasegawa Y, Nawata H (2000) Inhibin-like immunoreactivity produced by the adrenal gland is circulating in vivo. Fukuoka Igaku Zasshi 91:8–20PubMedGoogle Scholar
  108. 108.
    Preeyasombat C, Sirikulchayanonta V, Mahachokelertwattana P, Sriphrapradang A, Boonpucknavig S (1992) Cushing’s syndrome caused by Ewing’s sarcoma secreting corticotropin releasing factor-like peptide. Am J Dis Child 146:1103–1105PubMedGoogle Scholar
  109. 109.
    Makrigiannakis A, Margioris AN, Chatzaki E, Zoumakis E, Chrousos GP, Gravanis A (1999) The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophin-releasing hormone from human endometrial stromal cells. Mol Hum Reprod 5:789–796Google Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2010

Authors and Affiliations

  • Athina Kaprara
    • 1
  • Kalliopi Pazaitou-Panayiotou
    • 1
  • Alexandros Kortsaris
    • 2
  • Ekaterini Chatzaki
    • 3
  1. 1.Anticancer Hospital ‘Theagenio’ThessalonikiGreece
  2. 2.Laboratory of BiochemistryDemocritus University of ThraceAlexandroupolisGreece
  3. 3.Department of Pharmacology, Faculty of MedicineDemocritus University of ThraceAlexandroupolisGreece

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