{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:45:56Z","timestamp":1787021156064,"version":"build-2736575974"},"reference-count":131,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T00:00:00Z","timestamp":1228953600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:p>\n                    Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin\u2010releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino\u2010acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF\n                    <jats:sub>1<\/jats:sub>\n                    and CRF\n                    <jats:sub>2<\/jats:sub>\n                    receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptor in the stress\u2010related endocrine (activation of pituitary\u2010adrenal axis), behavioral (anxiety\/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonists in blunting these stress\u2010related components. The importance of CRF\n                    <jats:sub>1<\/jats:sub>\n                    signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety\u2010depression in a subset of patients.\n                  <\/jats:p>","DOI":"10.1196\/annals.1410.007","type":"journal-article","created":{"date-parts":[[2009,11,6]],"date-time":"2009-11-06T09:56:38Z","timestamp":1257501398000},"page":"29-41","source":"Crossref","is-referenced-by-count":62,"title":["From Hans Selye's Discovery of Biological Stress to the Identification of Corticotropin\u2010 Releasing Factor Signaling Pathways"],"prefix":"10.1196","volume":"1148","author":[{"given":"Yvette","family":"Tach\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Brunnhuber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,11]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/138032a0"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-20-5-667"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.bmb.a073628"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-57-5-599"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-57-4-439"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.05883"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6267699"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm980426c"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6326264"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0202122"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2003.07.001"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419656"},{"key":"e_1_2_8_14_2","first-page":"928","volume-title":"Stress in Health and Disease. 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