Urocortins of the South African clawed frog, Xenopus laevis: conservation of structure and function in tetrapod evolution. Endocrinology 146

Several corticotropin-releasing factor (CRF) family genes have been identified in vertebrates. Mammals have four paralogous genes that encode CRF or the urocortins 1, 2, and 3. In teleost fishes, a CRF, urotensin I (a fish ortholog of mam-malian urocortin 1) and urocortin 3 have been identified, sug-gesting that at least three of the four mammalian lineages arose in a common ancestor of modern bony fishes and tet-rapods. Here we report the isolation of genes orthologous to mammalian urocortin 1 and urocortin 3 from the South Afri-can clawed frog, Xenopus laevis. We characterize the phar-macology of the frog peptides and show that X. laevis urocor-tin 1 binds to and activates the frog CRF1 and CRF2 receptors at picomolar concentrations. Similar to mammals, frog uro-cortin 3 is selective for the CRF2 receptor. Only frog urocortin 1 binds to the CRF-binding protein, although with signifi