Feeding-induced stimulation of luteinizing hormone secretion in male rhesus monkeys is not dependent on a rise in blood glucose concentration

Recent studies have suggested a role for glucose availability in the central control of reproductive function. Various experimental paradigms have shown that a large pharmacological reduction in circulating or cellular glucose levels can suppress LH secretion, ovulation, and reproductive behavior. In contrast, states of undernutrition, which are also associated with a suppression of reproductive function, are accompanied by very mild changes in circulating glucose levels. In monkeys, 1 day of fasting leads to a significant suppression of LH secretion before any significant change in blood glucose levels, and by 2 days of fasting, circulating glucose levels only decrease by about 20%. Refeeding a normal meal after 2 days of fasting results in a restoration of euglycemia and a rapid stimulation of LH secretion. To test the hypothesis that physiological changes in glucose levels occurring during brief periods of fasting and refeeding can modulate LH secretion, we provided monkeys that had been fasted for 2 days with meals that differed in the ability to raise blood glucose levels. Meals consisting of mixed nutrients, carbohydrate only, or protein and fat were provided to monkeys through indwelling gastric cannulas. Mixed nutrient infusions and carbohydrate infusions caused a rise in blood glucose as well as a robust stimulation of LH secretion. However, protein and fat meals also stimulated LH secretion, even though no rise in blood glucose concentrations occurred. Thus, the restoration of pulsatile LH secretion when fasted animals are refed is not dependent on an elevation in circulating glucose levels. These results do not support the hypothesis that physiological changes in circulating glucose levels play a necessary role in mediating the changes in LH secretion that occur with fasting and refeeding. Alternatively, these results support the hypothesis that the availability of metabolizable fuels, regardless of their nature, provides a critical cue that regulates the central drive to the reproductive axis under physiological conditions of fasting and feeding.