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In vertebrates, genome duplications led to the divergence of CRH receptors into CRH1 and CRH2 forms in tandem with the development of four paralogous ligand lineages that included CRH; urotensin I\/urocortin (Ucn), Ucn2 and Ucn3. In addition, taxon-specific genome duplications led to further local divergences in CRH ligands and receptors. Functionally, the CRH ligand\u2013receptor system evolved initially as a molecular system to integrate early diuresis and nutrient acquisition. As multicellular organisms evolved into more complex forms, this ligand\u2013receptor system became integrated with the organismal stress response to coordinate homoeostatic challenges with internal energy usage. In vertebrates, CRH and the CRH1 receptor became associated with the hypothalamo-pituitary\u2013adrenal\/interrenal axis and the initial stress response, whereas the CRH2 receptor was selected to play a greater role in diuresis, nutrient acquisition and the latter aspects of the stress response.<\/jats:p>","DOI":"10.1530\/jme-13-0238","type":"journal-article","created":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T01:17:36Z","timestamp":1396919856000},"page":"T43-T60","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":63,"title":["MOLECULAR EVOLUTION OF GPCRS: CRH\/CRH receptors"],"prefix":"10.1530","volume":"52","author":[{"given":"David A","family":"Lovejoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda S W","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R","family":"Lovejoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"del Castillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"13","key":"1_8989642","doi-asserted-by":"crossref","first-page":"8039","DOI":"10.1016\/S0021-9258(20)82024-9","volume":"258","author":"Aguilera","year":"1983","journal-title":"Journal of Biological Chemistry","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9258","issn-type":"print"},{"issue":"1","key":"2_34605246","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ygcen.2009.04.007","volume":"164","author":"Alderman","year":"2009","journal-title":"General and comparative endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-6480","issn-type":"print"},{"issue":"5394","key":"3_6246488","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1126\/science.282.5394.1711","volume":"282","author":"Amores","year":"1998","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"issue":"4","key":"4_33850836","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1080\/10635150600755453","volume":"55","year":"2006","journal-title":"Systematic Biology","ISSN":"https:\/\/id.crossref.org\/issn\/1063-5157","issn-type":"print"},{"issue":"1","key":"5_11018764","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1210\/en.142.1.446","volume":"142","author":"Arai","year":"2001","journal-title":"Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0013-7227","issn-type":"print"},{"key":"6_47936014","first-page":"87","volume":"113","year":"1994","journal-title":"General and comparative endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0016-6480","issn-type":"print"},{"issue":"2","key":"7_16443732","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0165-3806(95)00158-1","volume":"91","author":"Avishai-Eliner","year":"1996","journal-title":"Brain research. 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