Effects of polypeptide YY3-36 upon luteinizing hormone-releasing hormone and gonadotropin secretion in prepubertal rats: In vivo and in vitro studies

Abstract

Polypeptide YY3-36 (PYY3-36) is a gastrointestinal secreted molecule, agonist of neuropeptide Y (NPY) receptor subtypes Y 2 and Y5, recently involved in the control of food intake. Notably, several factors with key roles in energy homeostasis conduct pleiotropic effects upon the reproductive axis. However, whether PYY 3-36 is provided with similar biological actions remains so far largely unexplored. To address this issue, expression analyses of neuropeptide Y receptor Y2 and Y5 genes were conducted at the pituitary and the hypothalamus, and functional studies testing the effects of PYY 3-36 in vivo and in vitro were implemented, using the prepubertal rat as a model. Expression of the genes encoding Y2 and Y5 receptors was demonstrated, albeit at low levels, in whole hypothalamic and pituitary samples, and challenge of pituitary tissue with increasing doses of PYY3-36 elicited LH and FSH secretion in male and female rats, a response that was persistently observed in the absence of extracellular calcium. Moreover, 10-6 M PYY3-36 enhanced LH and FSH responsiveness to LHRH in vitro. In contrast, systemic ip administration of PYY3-36 over a range of doses (3, 10, and 30 μg/kg) failed to significantly modify serum LH levels in males and females, whereas central (intracerebroventricular) injection of 3 nmol PYY3-36 inhibited LH secretion in vivo, and 10-6 M PYY3-36 decreased LHRH release by hypothalamic fragments in vitro in male but not in female rats. Overall, our data document the complex mode of action of the gut-derived anorexigenic signal PYY3-36 at the hypothalamic-pituitary unit in the control of gonadotropin secretion and evidence that, as is the case for other peripheral factors with key roles in energy balance (as leptin and ghrelin), PYY3-36 might play a role in the neuroendocrine modulation of the reproductive axis.