The broad objective of this research proposal is to determine the mechanism by which changes in nutrient intake modify reproductive function in primate species. Studies to date indicate that reproductive dysfunction in undernourished human and nonhuman primates results primarily from inadequate secretion of GnRH from the hypothalamus; however, the physiological mechanism by which activity of GnRH-secreting neurons is linked to nutrient intake remains unknown.
The first aim of this proposal is to identify the physiological signal which couples GnRH secretion to the nutritional status of the body. Preliminary experiments suggest that protein availability may modify GnRH secretion. To examine this possibility, castrated male monkeys will be fed isocaloric, protein-deficient diets and changes in gonadotropin secretion, the response to GnRH, and the metabolic sequelae of protein deficiency will be examined. Other diets with isolated deficiencies of fat or carbohydrates will also be studied. Additional experiments will be performed to determine whether specific metabolic substrates and hormones, whose levels change during altered nutrient intake, are responsible for suppressing GnRH secretion.
The second aim i s to determine whether suppression of GnRH-neuronal activity during altered nutrient intake requires neuronal input from outside the medial basal hypothalamus (MBH; the hypothalamic region which is capable of sustaining gonadotropin secretion in monkeys after complete deafferentation from rest of the CNS). To address this question, changes in gonadotropin secretion during altered nutrient intake will be examined in monkeys with MBH deafferentations.
The third aim of this proposal is to determine whether changes in neurotransmitter secretion play a role in suppressing GnRH-neuronal activity during altered nutrient intake. Rates of NE, DA, and 5-HT synthesis as well as concentrations of these and other neurotransmitters and their metabolites will be compared in MBH tissues from monkeys eating normal diets and diets which lead to suppression of GnRH secretion. Elucidation of the mechanism by which nutrient intake modifies GnRH secretion will increase our understanding of 1) the physiological regulation of GnRH secretion, 2) why reproductive dysfunction occurs in states of altered nutrition (i.e. protein-calorie deprivation, weight loss, anorexia nervosa), and 3) the general question of how changes in the nutritional status of the body affect brain function.
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