Discussion New insights into urotensin endocrinology: From fish to man Catherine McCrohan a , Nicholas Bernier b a Faculty of Life Sciences, University of Manchester, 1.124 Stopford Building, Oxford Road, Manchester M13 9PT, UK b Department of Integrative Biology, University of Guelph, 50 Stone Road East, Guelph, Canada N1G 2WI The urotensins (UI and UII) were first identified in the cau- dal neurosecretory system (CNSS) of fish, a unique neuroen- docrine structure located in the terminal segments of the spinal cord. More recently, homologues to both peptides have been identified in mammals and, while research continues into the role of the CNSS in fish, interest in the actions of the uro- tensins in other vertebrates, including man, has grown. Steve Douglas reviewed the history of UII research in mammals, following the identification of its ‘‘orphan’’ G- protein coupled UT receptor, GPR14. Both UII and UT receptor are localised in regions of the mammalian brain, as well as in non-neural tissues such as cardiovascular and renal tissues. The potent vasoconstrictor actions of UII led to the search for antagonists that might be effective in dis- ease states such as hypertension, congestive heart failure and diabetes mellitus. Current animal studies give cause for optimism that this ‘‘from gills to pills’’ approach will lead to novel and improved clinical tools, such as in patients whose hypertension cannot currently be controlled. For example, UT receptor antagonists have been shown to be highly protective against heart failure in animal models. Continuing on this theme, Nick Ashton and Alaa Abdel-Razik reported renal effects of UII in the rat. UT receptors are present in renal medulla and UII appears in relatively high concentrations in urine, suggesting that it is actively secreted. Both haemodynamic and tubular actions of UII are indicated, leading to reduced urinary output, and the converse effects were seen with a UT receptor antagonist, urantide. Isabelle Lihrmann gave a comparative overview of UII, UII-related peptide (URP) and UT receptor distribution throughout the vertebrates. mRNA expression profiles for UII appear to be well conserved throughout the verte- brate series from dipneusts to mammals, with the highest level of expression in spinal cord, localised to motoneurons in the ventral horn. A similar distribution is seen for URP expression, apart from some differential expression in cra- nial nuclei. The UT receptor is widely expressed in the CNS and peripheral tissues, including skeletal muscle. In addition to central actions of the peptides with respect to cardiovascular control, these findings perhaps support a locomotory role for UII. In addition a role for URP in arousal, via the reticular activating system, was proposed. Jean-Claude Le Mevel reported investigations into the central actions of UI and UII. The two peptides had differ- ential effects when injected intracerebroventricularly in trout. UI, but not UII, caused increases in blood pressure and ventilatory output. Both peptides enhanced locomotor activity (swimming), though effects of UII were more long lasting. These findings suggest that the urotensins have important regulatory functions within the brain, which may also be of relevance to mammalian studies. A comparative genomics study by Herve Tostivint, examined the relationship between UII/URP and somato- statin (SS)-related peptides, previously considered to be unrelated gene products. These peptides display a similar cyclic structure and precursor organisation throughout the vertebrates. Analysis of predicted gene duplications and chromosomal locations has led to an evolutionary model supporting a single ancestral gene superfamily for UII- and SS-related genes, raising questions regarding the evolution of UII and its function in lower vertebrates. The CNSS of teleost fish was presented as a model system in which to examine neurosecretory mechanisms and uroten- sin physiology. In zebrafish (Caroline Parmentier), neurose- cretory Dahlgren cells display immunoreactivity for both UI and UII. Most cells do not colocalise the two peptides. However, in some, UI and UII are colocalised even at the level of secretory terminals and vesicles. Detailed morpho- logical observations indicate further secretory roles for the CNSS that have yet to be defined. With its characterised genome, the zebrafish provides the genetic tools with which to dissect CNSS function and other functional aspects of urotensin-related physiology. Sarah Alderman described a tissue mapping study of the expression patterns of UI, cor- ticotropin-releasing factor (CRF), and CRF-binding protein in adult and developing zebrafish. All three show widespread but highly localised distribution within the CNS, including 0016-6480/$ - see front matter Ó 2007 Published by Elsevier Inc. doi:10.1016/j.ygcen.2007.06.008 www.elsevier.com/locate/ygcen General and Comparative Endocrinology 153 (2007) 241–242