Endocrine Abstracts

The cardiovascular properties of the natriuretic peptide family of hormones are well-characterised, and provide valuable prognostic indicators in the treatment of heart failure in humans and companion animals. Of the three main mammalian natriuretic peptides, C-type natriuretic peptide (CNP) remains the most enigmatic, even though CNP represents the ancestral natriuretic peptide from which Atrial- (ANP) and B-type (BNP) natriuretic peptides evolved through gene duplication. We have focussed our studies on the role of CNP in the anterior pituitary gland and areas of the CNS, as these tissues represent major sites of expression of the peptide, and biological function, as established through pharmacological studies of the CNP-selective guanylyl cyclase B (GC-B) receptor. Using several biological models (humans, rodents, cell lines, Zebrafish and cats), we have started to establish the developmental profile of the CNP system in the pituitary, and have identified novel target genes downstream of CNP signalling. The genetically-tractable Zebrafish has proved an invaluable tool in the regard; we have cloned four separate CNP genes, each with subtly different spatiotemporal expression profiling, but all present within the CNS. We have developed multiplex RT-PCR assays to quantitate changes in these transcript levels, but also those of pituitary hormone markers, and found that exposure of developing Zebrafish larvae to exogenous CNP causes significant changes in pituitary hormone transcripts. Our in vitro studies, using gonadotroph-derived cell lines, suggest that components of the natriuretic peptide system are sensitive to pulsatile stimulation by gonadotrophin releasing hormone. Finally, our studies using astrocyte cell lines have revealed that CNP signalling is significantly inhibited by exposure to pathological concentrations of ammonia, mimicking conditions seen in patients with liver disease. These ongoing studies increase our understanding of the diverse role that CNP plays within neuroendocrine and CNS tissues.