GH AND IGF-I TREATMENT OF ELDERLY WOMEN

描述(摘自申请者摘要)：生长激素(GH) 在正常衰老过程中，分泌物减少，导致循环减少。 胰岛素样生长因子(IGF-1)水平。虽然生理学上 促生长激素功能下降的后遗症尚不完全清楚，许多 正常衰老所见的分解代谢变化，包括骨量减少、肌肉 萎缩和运动耐力下降的部分原因可能是 GH-IGF-I轴作用减弱。与年龄相关的人口数量下降 下丘脑-促生长激素-胰岛素样生长因子轴的活动可能因此导致 分解代谢素质导致老年人跌倒、骨折和虚弱， 一种已被命名为“躯体更年期”的综合征。以前的工作 已证明GH和IGF-I可减少脂肪质量，增加苗条的身体 质量和氮的滞留，并促进全身和骨骼肌网 蛋白质合成。 生长激素和高剂量IGF-1均可增加重塑骨小体的出生率。 然而，小剂量的IGF-I可能会直接增加成骨功能，而不是 增加骨吸收，因此可能提供一种有用的手段 增加骨量。此外，IGF-I可能具有改善心境的作用。 老年人。为了确定延长GH和IGF-I的影响 并了解其潜在的内分泌机制 生理学效应，三个独立的生理学研究 提出生长激素和胰岛素样生长因子-I治疗在躯体更年期中的作用。在这些 研究中，重点将放在了解相互作用上 雌激素/孕激素替代疗法(HRT)和治疗 躯体更年期。研究1为期一年，双盲，随机， 将探索生长激素、胰岛素样生长因子-I相互作用的安慰剂对照试验 和雌激素/孕激素治疗对身体成分、肌肉力量和 肌肉生长因子合成。研究II将探索内分泌机制 生长激素和胰岛素样生长因子-I治疗对大鼠脑室积液的影响 细节。这项实验将建立在先前研究的基础上，这些研究出人意料地 证明了这两种荷尔蒙都会引起水的戏剧性变化 细胞内空间。研究III是一项短期研究，将考察 GH和IGF-1在蛋白质和脂代谢中的作用 这些激素在老年妇女体内的合成代谢作用。这项研究将会有所帮助 为研究I中的发现提供了一个机制基础。 研究将首次对激素的相互作用进行研究。 躯体更年期(GH和IGF-I)和更年期的替代疗法 (雌激素和孕激素)，并将导致新的药物治疗方法 治疗老年人的虚弱。

DESCRIPTION (Adapted from the Applicant's Abstract): Growth hormone (GH) secretion declines during normal aging, resulting in lower circulating levels of insulin-like growth factor (IGF-1). Although the physiologic sequelae to decreased somatotrope function are not fully understood, many of the catabolic changes seen in normal aging, including osteopenia, muscle atrophy, and decreased exercise tolerance, may in part be caused by the decreased action of the GH-IGF-I axis. The age-related decline in the activity of the hypothalamic-somatotrope-IGF axis may thus result in catabolic diathesis leading to falls, fractures, and frailty in the elderly, a syndrome complex which has been named "the somatopause". Previous work has demonstrated that GH and IGF-I decrease fat mass, increase lean body mass and nitrogen retention, and promote whole body and skeletal muscle net protein synthesis. Both GH and high dose IGF-1 increase the birthrate of remodeling osteons. However, low-dose IGF-I may directly increase osteoblastic function without increasing bone resorption, and may therefore provide a useful means to increase bone mass. Moreover, IGF-I may have mood-enhancing effects in the elderly. In order to determine the effects of prolonged GH and IGF-I therapy and to understand the endocrine mechanisms underlying their physiologic effects, three independent investigations into the physiologic role of GH and IGF-I therapy in the somatopause are proposed. In these studies, a major emphasis will be placed on understanding the interactions of estrogen/progestin hormone replacement therapy (HRT) and treatment of the somatopause. Study 1 is a year long, double-blind, randomized, placebo-controlled trial which will explore the interactions of GH, IGF-I and estrogen/progestin therapy on body composition, muscular strength, and muscle growth factor synthesis. Study II will explore endocrine mechanisms underlying the effects of GH and IGF-I therapy on fluid compartments in detail. This experiment will build upon previous studies which unexpectedly demonstrated that both hormones cause dramatic shifts of water into the intracellular space. Study III is a short term study that will examine the role of GH and IGF-1 in protein and lipid metabolism to understand the anabolic action of these hormones in elderly women. This study will help provide a mechanistic basis for the finding obtained in Study I. These studies will provide the first investigation of the interactions of hormone replacement therapies for the somatopause (GH and IGF-I) and the menopause (estrogen and progestin) and will lead to novel pharmacologic approaches for the treatment of frailty in the elderly.