THE INSULIN HYPOGLYCEMIA-INDUCED INHIBITION OF GONADOTROPIN-RELEASING-HORMONE PULSE-GENERATOR ACTIVITY IN THE RHESUS-MONKEY - ROLES OF VASOPRESSIN AND CORTICOTROPIN-RELEASING FACTOR

Insulin-induced hypoglycemia (IIH) profoundly inhibits the activity of the hypothalamic GnRH pulse generator. The aim of this study was to d etermine the role of vasopressin and CRF in this response. Ovariectomi zed rhesus monkeys with chronically implanted recording electrodes in the mediobasal hypothalamus and with intracerebroventricular (icv) can nulas in the lateral ventricle were placed in primate chairs, and bloo d samples were taken every 10 min. Pulse generator activity was monito red electrophysiologically by detecting characteristic increases in hy pothalamic multi-unit activity (MUA volleys) and by attendant LH pulse s measured in peripheral blood. Arginine vasopressin (AVP) infused via the icv cannula (50 mu g/60 mu l . h) in eight monkeys failed to decr ease pulse generator activity, as measured by the frequency of MUA vol leys, but decreased mean serum LH concentrations (P < 0.001) while inc reasing serum cortisol levels (P < 0.02). Central administration of an AVP antagonist ([deamino-Pen(1),O-Me-Tyr(2),Arg(8)] vasopressin) in f our monkeys at a rate (180 mu g/60 mu l . h) that had previously been found to block the aforementioned effects of coadministered AVP failed to prevent the IIH-induced inhibition of GnRH pulse generator activit y and LH secretion in the same animals. On the other hand, a CRF antag onist, [D-Phe(12),Nle(21,38),C alpha MeLeu(37)]rat CRF-(12-41), infuse d icv at a rate of 500 mu g/60 mu l . h in four monkeys, delayed the i nhibition of pulse generator frequency in response to IIH. These resul ts suggest that AVP does not mediate the hypoglycemia-induced inhibiti on of GnRH pulse generator frequency in the rhesus monkey, but that CR F may be involved in this response.