The influence of endogenous growth hormone (GH) on body composition and the mechanisms involved in the decline in GH secretion and changes in body composition associated with increasing age will be studied in human adults. While the effects of GH administration to adults on body composition are known from short-term studies of a few GH deficient and older adults, the neuroendocrine factors responsible for the decline in GH secretion in adults have not been identified. It is necessary to identify these factors to define the role of pharmacologic therapies which may restore endogenous GH secretion to that of a young adult. Alternatively, if exogenous GH is to be administered to adults, the pattern of GH delivery which produces the optimal metabolic effects needs to be determined. The proposed studies are designed to: (a) elucidate the mechanisms responsible for the decline in GH secretion with aging, (b) define the relationship between GH secretion and body composition, (c) determine if pharmacologic agents can restore GH secretion in aging subjects to that of young subjects, and (d) determine the optimal method of GH administration. Hypothesis 1: Decreased GH secretion in aging results from decreases growth hormone releasing (GHRH) secretion and/or enhanced somatostatin (SS) secretion and/or increased sensitivity to insulin-like growth factor I (IGF-I). Several pharmacologic agents will be used to identify the factor(s) resulting in decreased GH secretion in the elderly: GHRH, pyridostigmine (inhibits SS secretion) clonidine (stimulates GHRH secretion), somatostatin (excessive SS secretion) and IGF-1 (somatotrope sensitivity to negative feedback). Hypothesis 2: GH deficient young adults and healthy older adults will have similar decrements in GH secretion and changes in body composition compared with healthy young subjects. The relationship between pulsatile GH secretion, assessed using a sensitive GH assay, and body muscle, fat, water content and bone density will be determined in GH deficient and older adults. Hypothesis 3: Endogenous GH secretion can be enhanced in older men and women with specific medical therapies: 1) oral and transdermal estradiol (postmenopausal women); 2) continuous GHRH administration, and 3) oral growth hormone releasing peptide (GHRP).
Showing the most recent 10 out of 73 publications
