NPY and pituitary function

NPY antagonists for the treatment of obesity should be without effects on the hypo-thalamic-pituitary-adrenal (HPA) and growth hormone (GH) axes. There is increasing evidence that the receptors mediating NPY effects on feeding and pituitary function are different, but further research is needed to clarify this. 

It is thought that the effect of NPY on GH is not direct, rather it is mediated through its ability to stimulate the release of hypothalamic somatostatin. Synaptic associations exist between NPY containing and somatostatin containing neurons within the hypothalamus (Hisano et al., 1990). Low doses of NPY stimulate the release 

Strong evidence in favour of a regulatory role between NPY and GRF was recendy observed by Pierroz and co-workers. They found that chronic administration of NPY completely abolished normal pulsatile secretion of GH and consequendy halved plasma IGF-1 levels in the intact adult male rat within the 7 days of the experiment (Pierroz etal., 1996). 

In conclusion, most of the published data provides evidence consistent with a primary effect of NPY to inhibit GH secredon through an action on the release of somatostatin from the hypothalamus. 

It has been suggested that the full sequence of NPY is necessary for activation of the HPA axis. This suggestion was based solely on findings that in comparison to NPY, desamidated NPY or NPY (19-36) were inactive at stimulating ACTH release (Miura et al., 1992). Further studies are needed to characterize the receptor type involved. 

---