Inhibition of gonadotropin secretion in castrated male rhesus monkeys (Macaca mulatta) induced by dietary restriction: analogy with the prepubertal hiatus of gonadotropin release

Abstract

The purpose of this study was to examine further the notion that in higher primates, analogous neuroendocrine mechanisms may underlie the hiatus in LH and FSH secretion during prepubertal development and the suppression of gonadotropin release in adults during states of malnutrition. To this end, the metabolic sequelae and the gonadotropin response to restricted food intake (RFI) were determined in nine castrated male rhesus monkeys. The results obtained were then evaluated in light of current understanding of the neuroendocrine bases of the ontogeny of gonadotropin secretion in primates. A reduction in food intake from approximately 1150 Cal/day to approximately 200 Cal/day for 20-34 days resulted in declines in body weight and circulating LH and FSH concentrations. The reduction in body weight and the suppression of LH secretion were statistically significant (P less than 0.05). The decrease in gonadotropin secretion induced by RFI was fully restored by the chronic iv intermittent infusion of GnRH (0.1 microgram/min for 3 min every hour). These findings graphically demonstrate that RFI, or a sequelae of this nutritional perturbation, inhibits gonadotropin secretion, in the absence of feedback influences by gonadal hormones, by an action at a suprapituitary level that is mediated by interruption of intermittent hypothalamic GnRH discharge. The apparent arrest of the neural mechanism that governs the timing of intermittent GnRH discharge, the so-called GnRH pulse generator, was associated with decreases in plasma insulin (P = 0.078), T4 (P less than 0.05), and T3 (P less than 0.05) concentrations and with a significant (P less than 0.05) elevation in circulating cortisol levels. Although a general decrease in circulating amino acid levels was not observed during RFI, plasma glutamate concentrations were significantly (P less than 0.05) reduced by the nutritional perturbation. RFI resulted in unremarkable hypoglycemia. While the suppression of gonadotropin secretion in castrated male monkeys during RFI resembled, in certain aspects, the hiatus in gonadotropin secretion during prepubertal development, the endocrine and metabolic concomitants of these two physiological states exhibited important differences. Thus, the contemporary notion that the study of dietary restriction in adult primates may provide insights into the neuroendocrine mechanisms that govern the timing of the onset of puberty in these species should not be accepted without careful consideration.