IS GLUTAMATE-INDUCED REDUCTION IN GROWTH HORMONE-RELEASING HORMONE A NEUROENDOCRINE MODES OF AGING IN THE RAT

Decreases in serum growth hormone (GH) associated with aging may be a result of age-related degenerative changes in neurons of the hypothala mus resulting in a decrease of growth hormone-releasing hormone (GHRH) . This study tests the utility of glutamate-induced hypothalamic neuro nal degeneration in the rat as a neuroendocrine model of aging. Spragu e-Dawley female rats received three 4-mg/g monosodium glutamate (MSG) subcutaneous injections during the first 5 days following birth. Anima ls were anesthetized at 60 days of age and challenged with GHRH. Blood samples were assayed for GH. Serum GH levels following GHRH challenge in the MSG-treated group rose more slowly and to a lower peak than in controls (P < 0.05). There was no difference in total GH release over the 1-hr interval following challenge. MSG-treatment of animals resul ted in lower gross body (P < 0.05) and kidney (P < 0.05) weights with no difference in ovary or adrenal weights. There were also no differen ces in pituitary GH or total protein content between the groups. Analy sis of femurs in the MSG animals revealed both a lower bone strength ( P < 0.05) and maximum mid-shaft diameter (P < 0.05), but no difference in length, mineral/matrix ratio, or tissue density. Our data suggest that the degree of neuroendocrine disruption resulting from neonatal M SG administration mimics in part systemic changes commonly observed in aged animals. Hence, definite similarities exist between MSG treatmen t and the documented aging-related changes in hypothalamic GHRH conten t and GH regulation in the rat.