GH AND IGF-I TREATMENT OF ELDERLY WOMEN

生长激素（GH）分泌下降，在正常老化，导致 降低血清胰岛素样生长因子（IGF）-I水平。 虽然 这种生长激素功能下降的生理后遗症（ “somatopause”）还没有完全理解，很可能许多 在正常衰老中看到的分解代谢变化，包括骨质疏松症，肌肉 萎缩和运动耐量下降，部分原因是由于 降低GH-IGF-I轴的作用。 由于骨质疏松症是一个主要的 妇女的健康问题，这项建议将测试生长激素的影响， IGF-I在健康老年女性中的应用有助于阐明 “体停”的机制。 待检验的两个具体假设 本提案包括： 1. GH对身体成分的某些影响独立于 循环IGF-I。 当给予GH时，循环GH和IGF-1 水平上升，但当注入IGF-I时，GH被抑制。 GH治疗具有 一些严重的副作用，包括葡萄糖耐量下降 和发展。水肿和腕管综合症，并发症 这在IGF-I治疗中不太可能出现。 通过比较 GH与IGF-I注射的影响，将有可能了解哪些 代谢作用是由GH单独发挥的，无论是通过自身还是通过 组织IGF的生成。 这一目标将通过以下方式实现： A. GH与IGF-I治疗老年人的简短（6周）比较试验 B。IGF-I与GH治疗在安慰剂对照组中的作用比较 1年干预试验 2. GH或IGF-I治疗将与运动协同作用，以增加骨骼和 肌肉质量和改善血脂谱。 虽然运动会 增加肌肉质量在健康的老年人，在发展高原发生 14周后。 由于老年人在怀孕期间不会增加GH分泌， 运动到年轻受试者的水平，很可能增加 GH或IGF-I的运动方案在高原的时候会 进一步提高运动能力和肌肉的柔韧性。 以前的研究生长激素对身体成分的影响已经使用 其解释因流体变化而模糊的方法。 由于慢性 女性GH治疗引起大量液体转移， GH或IGF-I可能对身体有积极影响的可能性 合成将需要更复杂和精确的方法。 骨 密度和身体成分将通过双能X射线测量 吸收测定法 肌肉质量将通过监测直接评估 蛋白质利用率、V02 max和生活质量的变化 这些研究将提供一个合理的基础 选择生长激素或IGF-I来对抗衰老的分解代谢作用， 增强运动能力，增加肌肉力量和体力 健身

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.