Evidence That Neuropeptide Y Could Represent a Neuroendocrine Inhibitor of Sexual Maturation in Unfavorable Metabolic Conditions in the Rat

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior and reproductive function. Whereas central administration of NPY strongly stimulates feeding, diet restriction produces overexpression of NPY in the arcuate and paraventricular nuclei that might reflect behavioral adaptations to shortage of food. The role of NPY for the regulation of sexual function is still controversial. Whereas NPY is stimulatory during proestrus in the rat, acute administration of NPY is inhibitory in castrated animals and we have shown that chronic administration of NPY inhibits both the gonadotropic and somatotropic axis in adult female rats. In order to further analyse the role of NPY during sexual maturation, a model of delayed sexual maturation imposed by food restriction and return to ad-libitum feeding was used. Young female rats were restricted to 7-8 g food daily starting at 24 days of life (d). This restriction completely prevented sexual maturation. At 50 d, ICV cannulas were placed and at 60 d, Alzet minipumps either delivering NPY (18 micrograms/day) or vehicle into the ICV cannula were implanted dorsally. At 61 d, rats were switched to ad-libitum feeding, a change that produced vaginal opening within 4 days in all vehicle-treated rats. In the rats receiving NPY, significantly increased food intake and weight gain were observed but only one out of the 9 rats studied experienced vaginal opening at 66 d, the other 8 animals remaining sexually immature at 67 d at sacrifice. Sexual immaturity of NPY-treated rats was further confirmed by decreased ovarian weight and reduced number of pituitary GnRH receptors. Plasma IGF-I levels were markedly reduced in NPY-treated rats. Since food restriction has been shown both to increase hypothalamic NPY and to reduce or inhibit sexual function, these data bring evidence for the first time that NPY could be involved in the inhibition of sexual maturation imposed by food restriction, since maintenance of elevated NPY levels in the hypothalamus did prolong this state of sexual immaturity despite restoration of normal food intake.