GH AND IGF-I TREATMENT OF ELDERLY WOMEN

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Growth hormone (GH) secretion declines during normal aging, resulting in lower serum insulin-like growth factor (IGF)-I levels. Although the physiologic sequelae to this decline in somatotrope function (the "somatopause") are not fully understood, it is likely that many of the catabolic changes seen in normal aging, including osteoporosis, muscle atrophy, and decreased exercise tolerance, are in part caused by the decreased action of the GH-IGF-I axis. Since osteoporosis is a major health problem for women, this proposal will test the effects of GH and IGF-I administration in healthy elderly women to help elucidate the mechanism of the "somatopause". The two specific hypotheses to be tested in this proposal are: 1. GH exerts some of its effects on body composition independent of circulating IGF-I. When GH is administered, circulating GH and IGF-I levels rise, but when IGF-I is infused, GH is suppressed. GH therapy has a number of serious side-effects, including decreased glucose tolerance and the development. of edema and carpal tunnel syndrome, complications which are unlikely to appear with IGF-I therapy. By comparing the effects of GH vs. IGF-I injections, it will be possible to learn which metabolic effects are uniquely exerted by GH, either by itself or through the generation of tissue IGFs. This aim will be accomplished by: A. Brief (6 week) comparative trials of GH vs. IGF-I therapy in elders B. Comparing the effects of IGF-I vs. GH therapy in a placebo-controlled 1 year intervention trial 2. GH or IGF-I therapy will synergize with exercise to increase bone and muscle mass and improve serum lipid profiles. Although exercise will increase muscle mass in healthy elders, a plateau in development occurs after 14 weeks. Since elders do not increase GH secretion during exercise to the levels seen in young subjects, it is likely that adding GH or IGF-I to the exercise regimen at the time of the plateau will further enhance exercise performance and muscle anabolism. Previous studies into the effects of GH on body composition have used methods whose interpretation is obscured by fluid shifts. Since chronic GH therapy in women causes large fluid shifts, investigation of the possibility that GH or IGF-I may have positive effects on body composition will require more sophisticated i and precise methods. Bone density and body composition will be measured by dual energy x-ray absorptiometry. Muscle mass will be evaluated directly by monitoring changes in protein utilization, and V02 max and quality of life indicators will be assessed These studies will provide a rational basis for choosing GH or IGF-I to combat the catabolic effects of aging and to enhance the ability of exercise to increase muscle strength and physical fitness.