The overall goal of this study is to elucidate the physiological mechanisms by which short term changes in food intake lead to changes in the central neural drive to the reproductive axis in primate species. Previously, we have shown that brief periods of fasting (i.e., one to two days) lead to a significant suppression of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone secretion in adult male rhesus monkeys and men. Subsequent refeeding of monkeys after a brief period of fasting leads to a rapid and dramatic increase in LH and testosterone secretion within the first hour after meal intake. In the current grant, the first specific aim is to identify neuronal systems which may mediate the changes in LH secretion caused by fasting and refeeding. Experiments are examining the role of three specific neural systems in mediating nutrition-induced changes in LH secretion (A) the vagus nerves, (B) noradrenergic pathways, and (C) neuropeptid e Y (NPY)-containing neurons. The second specific aim is to determine the role of insulin and thyroid hormone (T3) in causing the suppression of LH secretion during fasting and the restoration of LH secretion during refeeding. The third specific aim is to determine the extent to which the diurnal pattern of LH secretion in the male rhesus monkey is determined by the pattern of daily food intake, and the timecourse with which changes in the pattern of food intake modify the pattern of LH secretion. Information provided by these studies is providing insight into the mechanisms by which reproductive function is suppressed in normal childhood, anorexia nervosa, bulimia nervosa, and with vigorous exercise training, in that these are all conditions where metabolic signals have been proposed to be at least partially responsible for the quiescent state of the reproductive axis. Studies completed this year have shown that NPY neurons throughout the hypothalamus are rapidly activated after miss ing a single meal, thus are in an ideal position to modulate changes in GnRH neuronal activity. FUNDING NICHD HD26888 PUBLICATIONS Caston-Balderrama AL, Cameron JL, Hoffman GE. Immunocytochemical localization of fos in perfused nonhuman primate brain tissue fixation and antisera selection. J Histochem Cytochem 46:547-556, 1998. Cameron JL. Fasting and reproduction in non-human primates. In Pennington Center Nutrition Series Nutrition and Reproduction (W Hansel, G Bray, DH Ryan, eds). Baton Rouge University of Louisiana Press, pp 95-109, 1998.
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