Evolution and physiology of the corticotropin-releasing factor (CRF) family of neuropeptides in vertebrates.

Corticotropin-releasing factor (CRF), urotensin-I, urocortin and sauvagine belong to a family of related neuropeptides found throughout chordate taxa and likely stem from an ancestral peptide precursor early in metazoan ancestry. In vertebrates, current evidence suggests that CRF on one hand, and urotensin-I, urocortin and sauvagine, on the other, form paralogous lineages. Urocortin and sauvagine appear to represent tetrapod orthologues of fish urotensin-I. Sauvagine's unique structure may reflect the distinctly derived evolutionary history of the anura and the amphibia in general. The physiological actions of these peptides are mediated by at least two receptor subtypes and a soluble binding protein. Although the earliest functions of these peptides may have been associated with osmoregulation and diuresis, a constellation of physiological effects associated with stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction have been identified in various vertebrate species. The elaboration of neural circuitry for each of the two paralogous neuropeptide systems appears to have followed distinct pathways in the actinopterygian and sarcopterygian lineages of vertebrates. A comparision of the functional differences between these two lineages predicts additional functions of these peptides.