A Possible Role of Neuropeptide Y as a Mediator of Undernutrition to the Hypothalamic Gonadotropin-Releasing Hormone Pulse Generator in Goats*

To understand central mechanisms for nutritional infertility, the activity of the GnRH pulse generator was directly assessed in ovariectomized (OVX) goats under several experimental conditions by recording characteristic increases in the multiple-unit activity (volleys). When estradiol (E(2))-treated animals were fasted for 4-5 days, the activity of the GnRH pulse generator was gradually suppressed, and the volley interval at the end of fasting was significantly prolonged, compared with that during the feeding period (67.4 vs. 49.3 min, n = 5, P < 0.01). On the other hand, such a significant effect on the pulse generator was not observed in OVX goats. In the second experiment, the animals received a bolus intracerebroventricular injection of several doses (0, 2, 5, and 20 microg/400 microl) of neuropeptide Y (NPY). Exogenous NPY dose-dependently inhibited the pulse generator activity. At the highest dosage, the 1st posttreatment volley interval was significantly longer than that of the pretreatment (112.4 vs. 32.6 min, n = 5, P < 0.01) in OVX goats. The suppressive effect of NPY was similarly observed in OVX+E(2) goats. Further, when NPY was infused (10 microg/200 microl.h for 6 h) into OVX goats, the activity of the GnRH pulse generator was almost completely inhibited during the infusion period. Hypothalamic sites responding to fasting were immunohistochemically evaluated using an antibody for Fos in castrated goats. Fos-immunoreactive neurons were found in areas adjacent to the third ventricle. Double-labeling immunohistochemistry revealed that a subpopulation of NPY neurons in the arcuate nucleus was activated in response to fasting. These results demonstrate that: 1) the activity of the GnRH pulse generator is suppressed by fasting in the presence of E(2); 2) exogenous NPY inhibits the activity of the GnRH pulse generator regardless of the presence of E(2); and 3) several hypothalamic neurons or regions, including those containing NPY in the arcuate nucleus, are activated by fasting. Collectively, these observations suggest that NPY acts as a mediator of undernutrition to the GnRH pulse generator.