Diets that are nutritionally inadequate delay and disrupt development of reproductive processes of immature experimental animals and humans, and impair function of the hypothalamic-pituitary-gonadal (HPG) axis in adults. Nutritional stress affects the HPG axis by reducing the serum concentrations of LH, FSH and gonadal steroids, and causes atrophy of primary and secondary sex organs. Gonadal/accessory sex organ atrophy and dysfunction during malnutrition result mainly from decreased concentrations of circulating gonadotropins. The reduced serum concentrations of LH and FSH during malnutrition appear to be a direct result of impaired gonadotropin secretion, rather than decreased synthesis and storage. The status of LHRH content in the entire hypothalamus or specific hypothalamic regions is uncertain at present. It appears from the few studies that have been coducted, however, that LHRH is present in normal levels, suggesting that LHRH release is impaired. These studies must be repeated and expanded before conclusions about LHRH synthesis, storage and release can be made. Using various recently developed in vivo and in vitro procedures, rat models and sensitive radioimmunoassays for measuring hormones of the hypothalamus (LHRH), the pituitary (LH, FSH, GH and prolactin) and the gonads (T and E2), careful studies of nutritional influences will be conducted on all levels of HPG axis. In addition, a new class of modulatory peptides, the endorphins, may be involved in the impairment of reproductive processes of nutritionally deprived animals. Techniques are currently available to study the interrelationships of the endorphins, nutrition and the HPG axis. The major objectives of the proposal are to: 1) determine if nutritional deficiencies affect hypothalamic LHRH content, distribution, release and bioactivity; 2) more carefully characterize pituitary LH and FSH storage, release and bioactivity during nutritional deficiencies; 3) determine which nutrients will reverse or prevent the impairments characterized in Objectives 1 and 2 and to determine the mechanisms of hormonal dynamics in which these nutrients function; 4) determine the effects of nutritional deficiencies on gonadotropin excretion and which nutrients prevent or reverse these effects.
|Badger, T M; Millard, W J; Owens, S M et al. (1991) Effects of gonadal steroids on clearance of growth hormone at steady state in the rat. Endocrinology 128:1065-72|