GONADAL STEROID EFFECT ON MYOFIBRILLAR PROTEIN SYNTHESIS

先前的研究表明，健康的老年人患糖尿病的几率较低 肌原纤维蛋白的合成比青壮年要多。这种蛋白质的变化 合成可能会对肌肉质量和功能产生不利影响。 恢复更年轻的肌原纤维蛋白合成速度 可能有助于减少与以下疾病相关的肌肉萎缩 衰老。因为衰老也与减少 性腺类固醇，而且因为有证据表明性腺类固醇 可能对肌肉有合成代谢作用，将进行研究，以检查 性腺激素替代治疗对肌原纤维蛋白代谢的影响 在60岁以上的健康志愿者中。这些研究旨在测试 几种假说：睾丸激素替代刺激肌原纤维 非SHBG结合的睾酮水平低的男性的蛋白质合成 阻断睾酮向双氢睾酮的转化不起作用 抑制睾酮对双氢睾酮的合成代谢作用 不抑制睾酮的合成代谢作用；雌激素替代 刺激绝经后妇女的肌原纤维蛋白合成 服用孕激素的同时补充雌激素可减弱这一效应 雌激素；睾丸激素刺激肌原纤维蛋白合成 绝经后妇女(给药剂量比男性小)； 性腺类固醇可增加组织中编码 丰富的肌原纤维蛋白。肌原纤维蛋白的合成将是 通过掺入稳定的同位素示踪剂来测定。肌原纤维 降解将通过3-甲基组氨酸的排泄来确定。级别 通过将肌肉RNA与特定的反义RNA杂交来确定mRNAs RNA探针。在这项研究中获得的基本知识可能有助于 阐明性腺类固醇是否可以作为一种 预防或逆转老年肌肉萎缩的综合策略。

Previous research shows that healthy older people have slower rates of myofibrillar protein synthesis than young adults. This change in protein synthesis could have adverse effects on muscle mass and function. Restoring a more youthful rate of myofibrillar protein synthesis potentially could help to minimize the muscle atrophy associated with aging. Because aging also is associated with decreased production of gonadal steroids, and because there is evidence that gonadal steroids could have anabolic effects in muscle, studies will be done to examine the effects of gonadal steroid replacement on myofibrillar protein metabolism in healthy volunteers over 60 years old. The studies are designed to test several hypotheses: that testosterone replacement stimulates myofibrillar protein synthesis in men with low non-SHBG-bound testosterone levels; that blocking conversions of testosterone to dihydrotestosterone does not inhibit the anabolic effect of testosterone to dihydrotestosterone does not inhibit the anabolic effect of testosterone; that estrogen replacement stimulates myofibrillar protein synthesis in postmenopausal women; that giving progestin along with the estrogen replacement attenuates the effect of estrogen; that testosterone stimulates myofibrillar protein synthesis in postmenopausal women (with a smaller dose than that given to men); that gonadal steroids increase tissue levels of the mRNAs that encode the abundant myofibrillar proteins. Myofibrillar protein synthesis will be determined by incorporation of a stable isotope tracer. Myofibrillar degradation will be determined by 3-methylhistidine excretion. Levels of mRNAs will be determined by hybridizing muscle RNA with specific antisense RNA probes. The basic knowledge gained in this study could help to elucidate whether gonadal steroids could be useful as part of a comprehensive strategy to prevent or reverse muscle atrophy in old age.