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 determine the role of vasopressin and CRF in this response. Ovariectomized rhesus monkeys with chronically implanted recording electrodes in the mediobasal hypothalamus and with intracerebroventricular (icv) cannulas in the lateral ventricle were placed in primate chairs, and blood samples were taken every 10 min. Pulse generator activity was monitored electrophysiologically by detecting characteristic increases in hypothalamic multi-unit activity (MUA volleys) and by attendant LH pulses measured in peripheral blood. Arginine vasopressin (AVP) infused via the i.c.v. cannula (50 micrograms/60 microliters.h) in eight monkeys failed to decrease pulse generator activity, as measured by the frequency of MUA volleys, but decreased mean serum LH concentrations (P < 0.001) while increasing serum cortisol levels (P < 0.02). Central administration of an AVP antagonist ([deamino-Pen1, O-Me-Tyr2-Arg8] vasopressin) in four monkeys at a rate (180 micrograms/60 microliters.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 activity and LH secretion in the same animals. On the other hand, a CRF antagonist, [D-Phe12,Nle21,38,C alpha MeLeu37] rat CRF-(12-41), infused i.c.v. at a rate of 500 micrograms/60 microliters.h in four monkeys, delayed the inhibition of pulse generator frequency in response to IIH. These results suggest that AVP does not mediate the hypoglycemia-induced inhibition of GnRH pulse generator frequency in the rhesus monkey, but that CRF may be involved in this response.
Chen
M D
MD
Department of Integrative Biology, University of Texas Medical School, Houston 77225, USA.
Ordög
T
T
O'Byrne
K T
KT
Goldsmith
J R
JR
Connaughton
M A
MA
Knobil
E
E
D000818:Animals; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D004566:Electrodes; D004594:Electrophysiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000503:physiopathology*; D007033:Hypothalamus, Middle / Q000502:physiology; D007328:Insulin; D007986:Luteinizing Hormone / Q000378:metabolism; D008253:Macaca mulatta; D010052:Ovariectomy; D051381:Rats; D014667:Vasopressins / Q000502:physiology*
D007328:Insulin; D014667:Vasopressins; D001127:Arginine Vasopressin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone