Chronic Administration of Neuropeptide Y into the Lateral Ventricle Starting at 30 Days of Life Delays Sexual Maturation in the Female Rat

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Abstract
The role of neuropeptide Y (NPY) in the regulation of sexual function is still controversial. Whereas central NPY administration is stimulatory during proestrus in the rat and other species, such administration is inhibitory in castrated animals and we have shown that chronic, central infusion of NPY inhibits both the gonadotropic and somatotropic axis in adult rats. Previous studies have suggested that NPY could be involved in the triggering of the first ovulatory LH surge and a recent report indicated that a single central NPY injection given at 30 days of life could advance sexual maturation. We therefore evaluated the effect of chronic NPY administration on the timing of sexual maturation in the female rat and compared the effects obtained with those induced by a single NPY injection. Constant infusion of NPY (18 µg/day) into the lateral ventricle delayed sexual maturation as seen by the absence of vaginal opening, delayed ovarian growth and reduced number of pituitary GnRH receptors. This inhibitory effect was seen as long as NPY was infused. In contrast, a single NPY injection either at 30 days of life or earlier, or repeated single injections between 28 and 31 days of life, did not modify the pace of sexual maturation. Unlike what is observed in adult animals, overall food intake was only minimally increased between 30 and 37 days of life in chronically NPY-infused rats, but this increase became more important thereafter. In acutely NPY-treated animals, the expected brisk acceleration of food intake in the 3 h following central NPY administration took place, and the amplitude of this acceleration increased significantly between 28 and 31 days of life. Plasma insulin-like growth factor levels were markedly reduced in all chronically NPY-treated rats, probably reflecting a decrease in GH secretion. These data demonstrate that elevated NPY levels in the hypothalamus can delay sexual maturation in normal female rats. The exact mechanism of action of NPY for this inhibitory action is still unclear: NPY could either display a specific inhibitory action on GnRH release or down-regulate NPY receptors involved in the mediation of the stimulatory action of NPY on the LH ovulatory surge in the rat.

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