Y2 receptor-selective agonist delays the estrogen-induced luteinizing hormone surge in ovariectomized ewes, but Y1-receptor-selective agonist stimulates voluntary food intake

Neuropeptide Y (NPY) plays a major role in the regulation of food intake, regulation of homeostasis, and neuroendocrine function. We have previously shown that third ventricular infusion of this peptide delays the estradiol benzoate-induced surge in LH secretion in ovariectomized ewes. To determine the receptor subtype that transmits this effect, we have now used the same model to infuse a Y1 receptor agonist [NPY Leu(31) Pro(34)], a Y2 receptor agonist (PYY3-36), and a Y4 receptor agonist (pancreatic polypeptide). We monitored the surges in animals given these agonists or artificial cerebrospinal fluid by measuring plasma LH levels, and we also measured daily voluntary food intake (VFI). A low (7 mug/h) dose of Y2 agonist delayed the surge but did not affect VFI, whereas a higher dose (14 mug/h) stimulated VFI. A dose of 18 mug/h of the Y1 agonist did not affect surge generation but also stimulated VFI. A dose of 24 mug/h of Y4 agonist affected neither surge generation nor VFI. These specificities are different from those reported for the rat and human (in which a Y2 agonist causes reduction in VFI). We conclude that, in sheep, the negative regulation of the reproductive axis by NPY and Y-receptor agonists is effected via the Y2 receptors, whereas the orexigenic effects are most likely effected via the Y1 receptors.