GROWTH HORMONE & SEX STEROID EFFECTS ON SKELETAL MUSCLE

生长激素

• 批准号: 3122978
• 负责人: Marc Roy Blackman
• 金额: $ 26万
• 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/3122978
• 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 function; muscle proteins; 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.

人类的衰老通常伴随着各种因素的逐渐减少。 生理功能，这在一些人身上导致了生理上的 损害，并最终可能导致残疾，从而恶化 生活质量和限制个人的独立性。现在就是 似乎与年龄有关的肌肉力量、步态和 平衡至少在一定程度上是可逆的。三个有据可查的 衰老过程的伴随是：(A)循环生长减少 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；和(C)身体成分改变， 减少肌肉质量，增加身体脂肪。最近的证据表明 用重组人生长激素(RhGH)或性激素治疗 可以改善一些老年人的身体成分，但 这种激素治疗(单独或联合治疗)对不同的 生理功能尚不清楚。我们假设：(A) 随着年龄的增长，生长激素、胰岛素样生长因子-I和性类固醇激素分别减少 和交互作用有助于减少骨骼肌质量和 老年女性的体力、体脂增加和有氧能力降低 以及(B)恢复正常生长激素、胰岛素样生长因子-I和性类固醇 联合激素治疗的状态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，我们建议在一个人口中证明 活动的、社区居住的、久坐不动的超过年龄的女人和男人 65岁，IGF-I和性类固醇水平低，行动不便， 用重组人生长激素、性激素进行6个月的激素治疗 (女性为雌激素/孕激素，男性为睾丸素)，或联合使用重组人生长激素 加用性类固醇，无论是单独的还是共同的，都会导致 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 荷尔蒙干预可以发挥其作用，使用 定量RNA模板特异性聚合酶链式反应技术检测 IGF-I、IGF-I受体和IGF-I结合蛋白基因表达的定量研究 骨骼肌活组织标本；以及(2) 后期分子事件和生理结局变量。应该 这项拟议的研究揭示了激素替代的有益效果，然后 将需要进行更长期的调查来检查相互作用 激素治疗与其他干预措施(如运动)相结合 条件反射)，以及它们对功能状态测量的影响 老年人口的增加。