Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: Ancient CRF paralogs

• Published in: Frontiers in neuroendocrinology Vol. 28; no. 1; pp. 1 - 27
• Main Authors: Fekete, Éva M, Zorrilla, Eric P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2007
• Subjects: Amino Acid Sequence; Animals; Anxiety - metabolism; Anxiety or depression; Cardiovascular or hypertension or heart failure; Cardiovascular System - metabolism; Corticotropin-releasing factor or CRF or corticotropin-releasing hormone or CRH or corticoliberin; Corticotropin-Releasing Hormone - chemistry; Corticotropin-Releasing Hormone - classification; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Eating; Endocrinology & Metabolism; Energy Metabolism; Evolution, Molecular; Female; Food intake or energy balance or obesity; Gastrointestinal Motility; Gastrointestinal motility or irritable bowel syndrome; Hearing - physiology; Humans; Hypothalamo-Hypophyseal System - physiology; Immune System - physiology; Inflammation or immune system; Labor or parturition; Molecular Sequence Data; Peptide; Phylogeny; Pregnancy; Receptors, Corticotropin-Releasing Hormone - genetics; Receptors, Corticotropin-Releasing Hormone - metabolism; Salt or fluid balance; Sequence Alignment; Stress response; Urocortin 1 or urocortin 2 or urocortin 3 or stresscopin or stresscopin-related peptide; Urocortins; Urocortin 1 or urocortin 2 or urocortin 3 or stresscopin or stresscopin-related peptide; Anxiety or depression; Pregnancy; Salt or fluid balance; Inflammation or immune system; Gastrointestinal motility or irritable bowel syndrome; Labor or parturition; Food intake or energy balance or obesity; Stress response; Peptide; Corticotropin-releasing factor or CRF or corticotropin-releasing hormone or CRH or corticoliberin; Cardiovascular or hypertension or heart failure
• ISSN: 0091-3022; 1095-6808
• DOI: 10.1016/j.yfrne.2006.09.002

Abstract Urocortins, three paralogs of the stress-related peptide corticotropin-releasing factor (CRF) found in bony fish, amphibians, birds, and mammals, have unique phylogenies, pharmacologies, and tissue distributions. As a result and despite a structural family resemblance, the natural functions of urocortins and CRF in mammalian homeostatic responses differ substantially. Endogenous urocortins are neither simply counterpoints nor mimics of endogenous CRF action. In their own right, urocortins may be clinically relevant molecules in the pathogenesis or management of many conditions, including congestive heart failure, hypertension, gastrointestinal and inflammatory disorders (irritable bowel syndrome, active gastritis, gastroparesis, and rheumatoid arthritis), atopic/allergic disorders (dermatitis, urticaria, and asthma), pregnancy and parturition (preeclampsia, spontaneous abortion, onset, and maintenance of effective labor), major depression and obesity. Safety trials for intravenous urocortin treatment have already begun for the treatment of congestive heart failure. Further understanding the unique functions of urocortin 1, urocortin 2, and urocortin 3 action may uncover other therapeutic opportunities.