GROWTH HORMONE & SEX STEROID EFFECTS ON SKELETAL MUSCLE

生长激素

• 批准号: 2052216
• 负责人: Marc Roy Blackman
• 金额: $ 28.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2052216
• 关键词: adipose tissue; aging; body composition; echocardiography; estrogens; exercise; heart function; hormone binding protein; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; human therapy evaluation; in situ hybridization; insulin receptor; insulinlike growth factor; magnetic resonance imaging; messenger RNA; muscle proteins; muscle strength; photon absorptiometry; physical fitness; polymerase chain reaction; progestins; protein biosynthesis; sex hormones; somatotropin; stable isotope double label; striated muscles; testosterone

Human aging is generally accompanied by a gradual decline in various physiological functions, which in some people results in physical impairments, and ultimately may cause disabilities which worsen the quality of life and limit the independence of the individual. It now appears that age-related disturbances in muscle strength, gait, and balance are at least partly reversible. Three well-documented accompaniments of the aging process are: (a) decreased circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I), (b) reduced plasma sex steroid hormone levels; and (c) altered body composition, with decreased muscle mass and increased body fat. Recent evidence suggests that treatment with either recombinant human GH (rhGH) or sex steroids can improve body composition in some older persons, but the effects of such hormonal treatment (singly or in combination) on various physiological functions are unknown. We hypothesize that: (a) the decreases in GH, IGF-I and sex steroids that occur with aging, separately and interactively contribute to diminished skeletal muscle mass and strength, increased body fat, and reduced aerobic capacity in older women and men; and that (b) restitution of normal GH, IGF-I and sex steroid status by combined hormone therapy will exert additive or synergistic effects to increase muscle mass, strength, and aerobic capacity, and decrease body fat. We therefore propose to demonstrate, in a population of ambulatory, community-dwelling, sedentary women and men beyond the age of 65, with low IGF-I and sex steroid levels, and reduced mobility, that 6-months of hormonal treatment with rhGH, sex steroid hormones (estrogen/progestin in women and testosterone in men), or combined rhGH plus sex steroids will, singly or together, result in improvements in certain physiological variables such as skeletal muscle mass and strength, total body protein synthesis, aerobic capacity and myocardial function. Additionally, we propose to examine (1) molecular mechanisms by which the hormonal interventions may exert their effects, using the quantitative RNA template-specific polymerase chain reaction technique to quantify mRNAs for IGF-I, IGF-I receptors and IGF-I binding proteins in skeletal muscle biopsy specimens; and (2) the relationships between the latter molecular events and the physiological outcome variables. Should the proposed study reveal beneficial effects of hormone replacement, then longer-term investigations will be warranted to examine the interactions of hormone treatment with other interventions (e.g. exercise conditioning), and their effects on functional status measurements, in additional populations of older people.

人类的衰老一般伴随着各种 生理功能，这在某些人中会导致身体 损伤，并最终可能导致残疾， 生活质量和限制个人的独立性。 现在 似乎与年龄有关的肌肉力量，步态， 平衡至少部分是可逆的。 三个证据确凿的 衰老过程的表现是：（a）循环增长减少 激素（GH）和胰岛素样生长因子-I（IGF-I），（B）降低血浆 性类固醇激素水平;以及（c）改变身体组成， 减少肌肉质量和增加身体脂肪。 最近的证据表明 用重组人生长激素（rhGH）或性类固醇治疗， 可以改善一些老年人的身体成分，但 这种激素治疗（单独或组合）对各种 生理功能未知。 我们假设：（a） 随着年龄的增长，GH、IGF-I和性类固醇分别减少， 并且交互地有助于减少骨骼肌质量， 老年妇女的力量，身体脂肪增加，有氧能力降低 和（B）恢复正常GH、IGF-I和性类固醇 联合激素治疗将发挥相加或协同作用 增加肌肉质量，力量和有氧能力的效果，以及 减少身体脂肪。 因此，我们建议证明，在一个人口 社区居住、久坐不动的老年妇女和男子 65岁，IGF-I和性类固醇水平低，活动能力降低， 6-使用rhGH、性类固醇激素进行激素治疗数月 （女性雌激素/睾酮和男性睾酮）或联合rhGH 加上性类固醇，单独或一起，将导致改善， 某些生理变量，如骨骼肌质量和 力量、全身蛋白质合成、有氧能力和心肌 功能 此外，我们建议研究（1）分子机制 激素干预可以发挥其作用，使用 定量RNA模板特异性聚合酶链反应技术， 定量IGF-I、IGF-I受体和IGF-I结合蛋白的mRNA， 骨骼肌活检标本;和（2）之间的关系， 后者的分子事件和生理结果变量。 应该 这项研究揭示了激素替代的有益作用， 需要进行更长期的研究，以检查 激素治疗与其他干预措施（如运动） 条件反射），以及它们对功能状态测量的影响， 更多的老年人。