The stimulatory effect of PYY3-36 on gonadotropin secretion is potentiated in fasted rats

Development and normal function of the reproductive axis requires a precise degree of body energy stores. Polypeptide YY3-36 (PYY3-36) is a gastrointestinal secreted molecule recently shown to be involved in the control of food intake with agonistic activity upon neuropeptide Y (NPY) receptor subtypes Y2 and Y5. Notably, PYY3-36 has been recently demonstrated as putative regulator of gonadotropin secretion in the rat. However, the “reproductive” facet of this factor remains to be fully elucidated. In this context, we report herein our analyses of the influence of the nutritional status on the effects of PYY3-36 upon GnRH and gonadotropin secretion. The major findings of our study are: (1) the stimulatory effect of central administration of PYY3-36 on LH secretion was significantly enhanced after fasting, and blocked by a GnRH antagonist; (2) besides central effects, PYY3-36 elicited LH and FSH secretion directly at the pituitary level; a response which is also augmented by fasting; (3) PYY3-36 inhibited GnRH secretion by hypothalamic fragments from male rats fed ad libitum, whereas a significant stimulatory effect was observed after fasting; (4) the increase in the gonadotropin responsiveness to PYY3-36 in fasting was not associated with changes in the expression of Y2 and Y5 receptor genes at hypothalamus and/or pituitary. In conclusion, our study extends our previous observations suggesting a relevant, mostly stimulatory, role of PYY3-36 in the control of gonadotropin secretion. Strikingly, such an effect was significantly enhanced by fasting. Considering the proposed decrease in PYY3-36 levels after fasting, the possibility that reduced PYY3-36 secretion might contribute to defective function of the gonadotropic axis after food deprivation merits further investigation.