GONADAL STEROID EFFECT ON MYOFIBRILLAR PROTEIN SYNTHESIS

性腺类固醇对肌原纤维蛋白合成的影响

• 批准号: 6323237
• 负责人: STEPHEN WELLE
• 金额: $ 22.77万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6323237
• 关键词: aging; clinical research; cyclic aminoacid; dihydrotestosterone; estrogens; gene expression; hormone regulation /control mechanism; hormone therapy; human old age (65+); human subject; messenger RNA; muscle cells; muscle metabolism; muscle proteins; muscle strength; myofibrils; postmenopause; progestins; protein biosynthesis; protein degradation; radiotracer; steroid hormone; testosterone

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.

先前的研究表明，健康的老年人患心脏病的几率较低