Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that has a major role in coordinating the stress response of the body by mediating hormonal, autonomic, and behavioral responses to stressors. CRF (originally called corticotropin- releasing hormone, although the International Union of Pharmacology designation is CRF) was identified through classic techniques of peptide sequencing (Vale et al. 1981). Subsequently, genes encoding three paralogs of CRF—urocortins 1, 2, and 3 (Ucn 1, Ucn 2, Ucn 3), were identified by modern molecular biologic approaches. Ucn 2 and Ucn 3 are also referred to as stresscopin-related peptide and stresscopin, respectively. CRF and the urocortins have been implicated in the modulation of multiple neurobiologic systems, including those that regulate feeding, anxiety and depression, hypothalamic-pituitary-adrenal (HPA) axis signaling, and EtOH consumption (Hauger et al. 2006; Heilig and Koob 2007; Ryabinin and Weitemier 2006; Smith and Vale 2006). CRF and the Ucn peptides produce their effects by binding to the G protein-coupled CRF type 1 (CRF1R) and CRF type 2 (CRF2R) receptors. CRF binds to both receptors, but has greater affinity for the CRF1R (Bale and Vale 2004; Fekete and Zorrilla 2007; Hauger et al. 2006; Pioszak et al. 2008).
