HORMONES, HORMONE RECEPTORS AND AGING.III--AGING AND HUMAN ENDOCRINE REGULATION

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Results of a study quantitating the effects of aging on the regulation of the hypothalamic-pituitary-adrenal axis were submitted and published in FY 91. This work showed that both spontaneous 24 h pulsatile and CRH- stimulated secretion of ACTH and cortisol were unchanged with age and responded similarly in young and old men to suppression with graded doses of dexamethasone. These data do not support the hypothesis, advanced by others, that age-related changes in body composition and metabolism are due to a loss of sensitivity of the hypothalamic-pituitary-adrenal axis to negative feedback by glucocorticoids with resultant glucocorticoid excess. We are currently investigating the relationship of GH deficiency to aging and testing the effectiveness of potential interventions for raising endogenous GH and IGF-I secretion in older people. A study of 24 hr pulsatile GH secretion, acute GH response to iv GHRH, and plasma IGF-I measurements, done before and after two weeks of twice daily GHRH injections, repeated at 2 different doses, has been completed in 10 old and 9 young men. We demonstrated that pulsatile GH secretion and serum IGF-I levels were low in older men, and increased into the range seen in normal young men after treatment with 2 mg of GHRH daily. A manuscript is in preparation. A similar study of the effects of continuous 24 h subcutaneous GHRH infusion in old vs. young men is in the final stages of completion. A study of the effects of 2 weeks of orally administered 50:50 arginine/lysine mixture on GH and IGF-I secretion in older men is also nearly complete.