PITUITARY GONADAL FUNCTION IN FASTING

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A 2-year clinical research and training program in the University of Virginia General Clinical Research Center will consist of at least two separate research areas concerning mechanisms of fasting-associated hypogonadotropism in men and women. The research and training program will be supervised by Dr. Johannes D. Veldhuis (Department of Internal Medicine/Division of Endocrinology and Metabolism, University of Virginia, Charlottesville,VA). In the first study (1st year), the ability of a gonadotropin-releasing hormone (GnRH) pulse generator to avert the hypogonadotropism of fasting will be tested in normal weight men. In additions, the role of endogenous opiate peptides will be evaluated in the same context. In the second study (1st and 2nd year), I will test the hypothesis that fasting increases the negative feedback actions of sex steroids on the gonadal axis, while amplifying their positive feedback effects on the growth hormone (GH) axis, in postmenopausal women. These studies may elicit later evaluation of other hypotheses, such as that fasting affects the female gonadal axis in a stage-of-the-menstrual cycle specific manner (2nd year). Analysis of gonadotropin (LH and FSH) and GH secretory patterns during fasting will be carried out using computer-assisted multiple-parameter deconvolution analysis. This novel biophysical, computer-assisted technique gives the opportunity to calculate the frequency, mass, amplitude, and duration of these hormone secretory episodes as well as estimate subject-specific hormone clearance rates. Examining the secretory pattern of gonadotropins during short-term fasting in men and women should provide important clues to understanding the pathophysiology of diet- and exercise-induced abnormalities in the human reproductive axis.