Urotensin I–CRF–Urocortins: A mermaid’s tail

From the individual perspective of the two authors who were long-time colleagues of Karl Lederis at the University of Calgary, the events and personal interactions are described, that are relevant to the discovery of Urotensin I (UI) in the Lederis laboratory, along with the concurrent discovery of Urotensin II (UII) in the Bern laboratory and corticotropin-releasing factor (CRF/CRH) in the Vale laboratory. The fortuitous sabbatical experiences that put Professors Lederis and Bern on the track of the Urotensins, along with the essential isolation paradigm that resulted in the complete sequencing and synthesis of UI and UII are summarized. The chance interaction between Drs. Vale and Lederis who, prior to the publications of the sequences of UI and CRF, realized the sequence commonalities of these peptides with the vasoactive frog peptide, sauvagine, is outlined. Further, the relationship between the pharmacological studies done with UI in the Calgary laboratory and the more recent understanding of the biology and receptor pharmacology for the entire Urotensin I–CRF–Urocortin peptide family is dealt with. The value of a comparative endocrinology approach to understanding hormone action is emphasized, along with a projection to the future, based on new hypotheses that can be generated by unexplained data already in the literature. Based on the previously described pharmacology of the UI–CRF–Urocortin peptides in a number of target tissues, it is suggested that the use of current molecular approaches can be integrated with a ‘classical’ pharmacological approach to generate new insights about the UI–CRF–Urocortin hormone family.