Central Actions of Neuropeptide-Y May Provide a Neuromodulatory Link between Nutrition and Reproduction1

Central injection of neuropeptide-Y (NPY) has been shown to attenuate secretion of LH in ovariectomized rats, rabbits, and monkeys. Several investigators have reported elevated concentrations of NPY in the central nervous system of undernourished animals. The relationship between nutrition and reproduction positions NPY as a potential neuromodulator involved in nutritionally induced changes in secretion of LH. Three experiments were conducted with the following objectives: 1) to examine the effects of NPY on secretion of LH in ovariectomized (OVX) ewes and the influence of estradiol-17 β (E) on these effects; 2) to determine whether NPY may act through direct effects on the pituitary to influence secretion of LH; and 3) to determine changes in concentrations of NPY in laterocerebro-spinal fluid (CSF) of food-restricted ewes compared to well-fed ewes. In Experiment 1, OVX ewes with s.c. implants of E (OVX + E, n = 4) or no steroid treatment (OVX, n = 4) were fitted with intracerebroventricular (i.c.v.) and jugular cannulae. One of 4 doses of porcine NPY (pNPY; 0, 0.5, 5, or 50 μg) was injected i.c.v. and blood samples were collected every 10 min for 4 h prior to and following i.c.v. injection. Blood serum was assayed for LH. The experiment was replicated four times such that each ewe received each dose of pNPY. Mean concentrations of LH as well as frequency and amplitude of pulses of LH were attenuated in response to i.c.v. injection of pNPY in a dose-related manner in both OVX and OVX + E ewes. In Experiment 2, ovary-intact ewes were injected 1ev. with 12.5 μg of pNPY (n = 3) or vehicle (n = 3), followed 15 min later by an iv, injection of 50 μg of GnRH. Blood samples were collected every 15 min for 2 h and blood serum was assayed for LII. Mean concentrations of Lii over time did not differ between pNPY and salinetreated ewes, In Experiment 3, CSF from well-nourished (FED; n = 3) and food-restricted (R; n = 2) ewes was collected and assayed for NPY. Concentrations of NPY in CSF were elevated by 6 wk in R ewes compared to FED ewes (p < 0.01), and remained elevated after 9 wk of food restriction followed by 3 wk of realimentation. We conclude that the link between undernutrition and reproductive function in sheep may involve NPY-mediated actions on GnRH secretion.