The overall goals of this study are to determine the circumstances during which changes in nutritional intake modulate the function of the reproductive axis and to understand the mechanism by which nutritional signals modulate reproductive axis activity. Over the past year we completed several studies designed to identify the neural route by which metabolic signals modulate activity of the GnRH neuronal system in monkeys. Our findings indicate that signals traveling via the vagus nerves are not playing a critical role in mediating nutrition-induced changes in the central drive to the reproductive axis. This finding was in contrast to one previous study in the rat, which had shown that fasting-induced suppression of LH secretion was prevented by gastric vagotomy, and suggests that there may well be species differences in the mechanism by which nutritional signals modulate reproductive axis activity. In contrast we have shown that noradrenergic neuronal activity is necessary for nutrition-induced modulation of LH secretion. In female monkeys we examined whether very mild changes in food intake (decreasing food intake by 20%) and moderate exercise (running 1 hour per day at a low speed) would sensitize the reproductive axis to the suppressive effects of psychological stress. We found that female cynomolgus monkeys that are on a mild diet and exercise regimen have normal menstrual cyclicity; however, when exposed to the psychological stress of moving to a novel environment they are twice as likely to develop menstrual irregularities compared to monkeys not on such a diet/exercise regimen. In that women with hypothalamic amenorrhea are often about 10% under average body weight and exercise moderately, these findings suggest that the diet and exercise regimen these women undertake may sensitize them to stress-induced suppression of reproductive function.
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