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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD014586-04A1
Application #
3312696
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1981-05-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Donaghue, K C; Badger, T M; Millard, W J et al. (1990) Absence of ultradian rhythm or diurnal variation in insulin-like growth factor-I in rats. Neuroendocrinology 52:1-8
Badger, T M (1986) Perifusion of anterior pituitary cells: release of gonadotropins and somatotropins. Methods Enzymol 124:79-90
Badger, T M; Lynch, E A; Fox, P H (1985) Effects of fasting on luteinizing hormone dynamics in the male rat. J Nutr 115:788-97
Badger, T M (1985) Effects of total parenteral nutrition on luteinizing hormone dynamics in the male rat. J Nutr 115:798-806