GH AND IGF-I TREATMENT OF ELDERLY WOMEN

生长激素(GH)的分泌在正常衰老过程中会下降，导致 降低血清胰岛素样生长因子(IGF)-I水平。尽管 这种促生长激素功能下降的生理后遗症( “躯体更年期”)还没有完全被理解，很可能许多 正常衰老中的分解代谢变化，包括骨质疏松症、肌肉 萎缩和运动耐力下降的部分原因是 GH-IGF-I轴作用减弱。由于骨质疏松症是一个主要的 妇女的健康问题，这项提案将测试GH和 胰岛素样生长因子-I在健康老年妇女中的应用 “躯体更年期”的机制。需要检验的两个具体假设 在这项建议中，有： 1.GH对身体组成的一些影响不依赖于 循环中的IGF-I。应用生长激素时，循环生长激素和胰岛素样生长因子-I 水平升高，但当注入IGF-I时，生长激素被抑制。生长激素疗法有 一些严重的副作用，包括糖耐量下降 以及它的发展。浮肿和腕管综合征，并发症 这些症状不太可能在IGF-I治疗中出现。通过比较 GH与IGF-I注射的效果，将有可能了解哪种 代谢效应是由生长激素本身或通过 组织IGF的产生。这一目标将通过以下方式实现： A.GH与IGF-I治疗在老年人中的简短(6周)对比试验 B.在安慰剂对照中比较IGF-I和GH治疗的效果 为期1年的干预试验 2.GH或IGF-I治疗将与运动协同作用，增加骨骼和 增加肌肉质量，改善血脂水平。尽管锻炼会 健康老年人肌肉质量增加，出现发育平台期 14周后。由于老年人不会增加生长激素分泌 达到年轻受试者的运动水平，很可能会增加 GH或IGF-I到高原时的运动养生法会 进一步提高运动成绩和肌肉合成代谢。 以前关于生长激素对身体成分影响的研究已经使用了 其解释因流体位移而变得模糊的方法。由于慢性 GH治疗在女性中引起大量液体移动，调查 生长激素或胰岛素样生长因子-I对人体有积极作用的可能性 作文需要更复杂的方法和精确的方法。骨 密度和身体成分将用双能x射线测量。 吸光度测定法。肌肉质量将通过监测直接评估 蛋白质利用率、最大摄氧量和生活质量的变化 将对这些指标进行评估，这些研究将提供合理的基础 选择GH或IGF-I来对抗衰老的分解代谢影响，并 增强锻炼能力，增加肌肉力量和体能 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.