Rossetti Michael L, Steiner Jennifer L, Gordon Bradley S
The Institute of Exercise Physiology and Wellness, The University of Central Florida, PO Box 161250, Orlando, FL 32816, United States.
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, United States.
Mol Cell Endocrinol. 2017 May 15;447:35-44. doi: 10.1016/j.mce.2017.02.031. Epub 2017 Feb 22.
Androgens significantly alter muscle mass in part by shifting protein balance in favor of net protein accretion. During various atrophic conditions, the clinical impact of decreased production or bioavailability of androgens (termed hypogonadism) is important as a loss of muscle mass is intimately linked with survival outcome. While androgen replacement therapy increases muscle mass in part by restoring protein balance, this is not a comprehensive treatment option due to potential side effects. Therefore, an understanding of the mechanisms by which androgens alter protein balance is needed for the development of androgen-independent therapies. While the data in humans suggest androgens alter protein balance (both synthesis and breakdown) in the fasted metabolic state, a predominant molecular mechanism(s) behind this observation is still lacking. This failure is likely due in part to inconsistent experimental design between studies including failure to control nutrient/feeding status, the method of altering androgens, and the model systems utilized.
雄激素通过改变蛋白质平衡,使其有利于净蛋白质积累,从而显著改变肌肉质量。在各种萎缩性疾病中,雄激素分泌减少或生物利用度降低(称为性腺功能减退)的临床影响很重要,因为肌肉质量的丧失与生存结果密切相关。虽然雄激素替代疗法通过恢复蛋白质平衡部分增加肌肉质量,但由于潜在的副作用,这不是一个全面的治疗选择。因此,开发不依赖雄激素的疗法需要了解雄激素改变蛋白质平衡的机制。虽然人类数据表明雄激素在禁食代谢状态下改变蛋白质平衡(合成和分解),但这一观察结果背后的主要分子机制仍然缺乏。这种失败可能部分归因于研究之间不一致的实验设计,包括未能控制营养/喂养状态、改变雄激素的方法以及所使用的模型系统。