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) g oats under several experimental conditions by recording characteristic incr eases 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 inter val at the end of fasting was significantly prolonged, compared with that d uring the feeding period (67.4 us. 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 intracer ebroventricular injection of several doses (0, 2, 5, and 20 mug/400 mul) of neuropeptide Y (NPY). Exogenous NPY dose-dependently inhibited the pulse g enerator activity. At the highest dosage, the Ist posttreatment volley inte rval 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 sim ilarly observed in OVX+E-2 goats. Further, when NPY was infused (10 mug/200 mul(.)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 evaluat ed using an antibody for Fos in castrated goats. Fos-immunoreactive neurons were found in areas adjacent to the third ventricle. Double-labeling immun ohistochemistry 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 containin g 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.