Alexander Sarah E, Gatto Briana, Knowles Olivia E, Williams Ross M, Fiebig Kinga N, Jansons Paul, Della Gatta Paul A, Garnham Andrew, Eynon Nir, Wadley Glenn D, Aisbett Brad, Hiam Danielle, Lamon Séverine
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.
Cardiometabolic Health and Exercise Physiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
J Physiol. 2024 Oct 11. doi: 10.1113/JP286803.
Testosterone, the major androgen, influences the reproductive and non-reproductive systems in males and females via binding to the androgen receptor (AR). Both circulating endogenous testosterone and muscle AR protein content are positively associated with muscle mass and strength in males, but there is no such evidence in females. Here, we tested whether circulating testosterone levels were associated with muscle mass, function, or the muscle anabolic response to resistance training in pre-menopausal females. Twenty-seven pre-menopausal, untrained females (aged 23.5 ± 4.8 years) underwent a 12-week resistance training programme. Muscle strength, size, power, and plasma and urine androgen hormone levels were measured. Skeletal muscle biopsies were collected before and after the training programme to quantify the effect of resistance training on AR content and nuclear localisation. Primary muscle cell lines were cultured from a subset (n = 6) of the participants' biopsies and treated with testosterone to investigate its effect on myotube diameter, markers of muscle protein synthesis and AR cellular localisation. Physiological levels of total testosterone were not associated with muscle mass or strength at baseline or with the changes in muscle mass and strength that occurred in response to resistance training in our cohort of pre-menopausal females. In contrast, bioavailable testosterone and the proportion of nuclear-localised AR were positively associated with skeletal muscle mass and strength in pre-menopausal females. In vitro, supra-physiological doses of testosterone increased myocyte diameter, but this did not occur via the Akt/mTOR pathway as previously suggested. Instead, we show a marked increase in AR nuclear localisation with testosterone administration in vitro. KEY POINTS: Total circulating testosterone was not related to muscle mass or strength before or after resistance training in pre-menopausal females. Bioavailable testosterone was positively related to exercise-induced muscle hypertrophy in pre-menopausal females. In vivo nuclear localisation of the androgen receptor was positively related to muscle mass in pre-menopausal females at baseline, but not to resistance training-induced hypertrophy. Testosterone treatment induced androgen receptor nuclear translocation but did not induce mTOR signalling in primary skeletal myocytes cultured from pre-menopausal female muscle.
睾酮是主要的雄激素，通过与雄激素受体（AR）结合影响男性和女性的生殖系统及非生殖系统。循环中的内源性睾酮和肌肉AR蛋白含量在男性中均与肌肉质量和力量呈正相关，但在女性中尚无此类证据。在此，我们测试了循环睾酮水平是否与绝经前女性的肌肉质量、功能或对阻力训练的肌肉合成代谢反应相关。27名未受过训练的绝经前女性（年龄23.5±4.8岁）接受了为期12周的阻力训练计划。测量了肌肉力量、大小、功率以及血浆和尿液中的雄激素激素水平。在训练计划前后采集骨骼肌活检样本，以量化阻力训练对AR含量和核定位的影响。从部分参与者（n = 6）的活检样本中培养原代肌肉细胞系，并用睾酮处理，以研究其对肌管直径、肌肉蛋白合成标志物和AR细胞定位的影响。在我们的绝经前女性队列中，总睾酮的生理水平在基线时与肌肉质量或力量无关，也与阻力训练引起的肌肉质量和力量变化无关。相比之下，生物可利用睾酮和核定位AR的比例与绝经前女性的骨骼肌质量和力量呈正相关。在体外，超生理剂量的睾酮增加了肌细胞直径，但并非如先前所认为的通过Akt/mTOR途径发生。相反，我们发现在体外给予睾酮后AR核定位显著增加。要点：绝经前女性在阻力训练前后，循环总睾酮与肌肉质量或力量无关。生物可利用睾酮与绝经前女性运动诱导的肌肉肥大呈正相关。雄激素受体的体内核定位在基线时与绝经前女性的肌肉质量呈正相关，但与阻力训练诱导的肥大无关。睾酮处理诱导雄激素受体核转位，但在从绝经前女性肌肉培养的原代骨骼肌细胞中未诱导mTOR信号传导。
