Selective role of neuropeptide Y receptor subtype Y2 in the control of gonadotropin secretion in the rat.

Different signals with key roles in energy homeostasis regulate the reproductive axis. These include neuropeptide Y and polypeptide YY(3-36), whose type Y(2) receptor is the most abundant of this family in the brain. We evaluated herein the putative roles of Y(2) receptors in the control of gonadotropin secretion by means of central administration of PYY(13-36) (agonist of Y(2) receptors) and BIIE 0246 (antagonist of Y(2) receptors) to intact and orchidectomized male rats. In addition, the ability of PYY(13-36) to elicit GnRH and gonadotropin secretion in vitro and the impact of fasting on LH responses to PYY(13-36) in vivo were also monitored. Central administration of PYY(13-36) significantly decreased the circulating levels of both gonadotropins, an effect that was observed in prepubertal and adult rats. Yet a dual action of Y(2) receptors in the control of male gonadotropic axis was evidenced as their activation induced 1) stimulation of gonadotropin responses to GnRH at the pituitary but 2) inhibition of GnRH secretion at the hypothalamus. Antagonization of Y(2) receptors failed to modify basal LH secretion in intact males either after being fed ad libitum or after being fasted. In contrast, their central blockade in orchidectomized rats evoked a significant increase in circulating LH and FSH level, suggesting the constitutive activation of Y(2) receptor in such stimulated conditions. In summary, our data evidence a complex mode of action of Y(2) receptors in the control of gonadotropic axis, with stimulatory and inhibitory actions at different levels of the system that are sensitive to the gonadal status.