Hypoglycemia does not affect gonadotroph responsiveness to gonadotropin-releasing hormone in rhesus monkeys

Hypoglycemia inhibits gonadotropin secretion in primates by an undefined mechanism. Some evidence suggests that hypoglycemia inhibits gonadotropin secretion independent of gonadotropin-releasing hormone (GnRH) inhibition. To this end, the effect of insulin-induced hypoglycemia on the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to graded doses of GnRH (25, 75, and 250 ng/kg) administered at 120-min intervals was determined in rhesus monkeys. A crossover design was employed such that each animal received GnRH under both hypoglycemic and euglycemic conditions. Experiments were performed in the follicular phase. Gonadotroph responsiveness to GnRH was quantified by determining the change in area under the LH (ΔAULHC) and FSH (ΔAUFSHC) curves that occurred in the first 60 min following each GnRH pulse. There was no statistical difference in ΔAULHC between euglycemic and hypoglycemic animals at any GnRH dose (25 ng/kg: p=0.19; 75 ng/kg: p=0.41; 250 ng/kg: p=0.46). Similarly, changes in AUFSHC following GnRH administration were comparable in euglycemic and hypoglycemic animals (25 ng/kg: p=0.59; 75 ng/kg: p=0.90; 250 ng/kg: p=0.33). We conclude that hypoglycemia had no effect on gonadotroph responsiveness to GnRH. These results are consistent with the conclusion that hypoglycemia inhibits gonadotropin secretion by acting primarily at the level of the hypothalamus to reduce GnRH secretion rather than affecting pituitary responsiveness to GnRH.