雄激素受体通过IGF-1/IGF-1R-PI3K/Akt-mTOR信号通路在抗阻训练和耐力训练诱导的肌肉肥大中起关键作用。
Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway.
作者信息
Yin Lijun, Lu Lin, Lin Xiaojing, Wang Xiaohui
机构信息
Department of Kinesiology, Shanghai University of Sport, 188 Hengren Road, Yangpu District, Shanghai, 200438 People's Republic of China.
出版信息
Nutr Metab (Lond). 2020 Mar 30;17:26. doi: 10.1186/s12986-020-00446-y. eCollection 2020.
BACKGROUND
Androgen receptor (AR) has been reported to play vital roles in exercise-induced increase of muscle mass in rats, but needs to be further verified and the mechanism behind remains unclear. As AR target genes, insulin growth factor-1 (IGF-1) and IGF-1 receptor (IGF-1R) promote muscle hypertrophy through activating PI3K/Akt- mammalian target of rapamycin (mTOR) pathway, a classic pathway of muscle hypertrophy. So the main purpose of this study was using AR antagonist flutamide to demonstrate AR's effect on training-induced muscle hypertrophy and its possible mechanism: IGF-1/IGF-1R- PI3K/Akt- mTOR pathway?
METHODS
Forty-eight Sprague Dawley male rats aged 7 weeks were randomly divided into six groups: control (C), flutamide (F), resistance training (R), resistance training plus flutamide (R + F), endurance training (E), and endurance training plus flutamide (E + F) groups. Flutamide was used to block AR in rats. Rats in R and R + F groups fulfilled 3 weeks of ladder climbing with progressively increased load, while E and E + F rats completed 3-week moderate intensity aerobic exercise on a treadmill. The relative muscle mass (muscle mass/body weight) of rats was detected. Serum levels of testosterone and IGF-1 of rats were determined by ELISA, and mRNA levels of IGF-1R and mTOR in muscles by real-time PCR. Protein levels of AR, IGF-1, IGF-1R, mTOR, PI3K, Akt, p-PI3K and p-Akt in muscles were detected by Western blot.
RESULTS
(1) The training-induced rise in the relative muscle mass and the expression levels of AR were only found in the gastrocnemius of R rats and in the soleus of E rats (selective muscle hypertrophy), which were blocked by flutamide. (2) Serum testosterone in the R and E rat were increased, and flutamide exerted no effect. (3) The levels of IGF-1, IGF-1R and mTOR as well as the activities of PI3K and Akt were enhanced selectively (in the gastrocnemius of R rats and in the soleus of E rats), which were reduced by flutamide. AR exerted an essential role in both resistance training and endurance training-induced muscle hypertrophy, which was mediated at least partly through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway.
背景
雄激素受体（AR）在运动诱导的大鼠肌肉量增加中发挥重要作用，但仍需进一步验证，其背后的机制尚不清楚。胰岛素生长因子-1（IGF-1）和IGF-1受体（IGF-1R）作为AR靶基因，通过激活PI3K/Akt-雷帕霉素哺乳动物靶蛋白（mTOR）途径促进肌肉肥大，这是肌肉肥大的经典途径。因此，本研究的主要目的是使用AR拮抗剂氟他胺来证明AR对训练诱导的肌肉肥大的影响及其可能的机制：IGF-1/IGF-1R-PI3K/Akt-mTOR途径？
方法
将48只7周龄的Sprague Dawley雄性大鼠随机分为6组：对照组（C）、氟他胺组（F）、抗阻训练组（R）、抗阻训练加氟他胺组（R+F）、耐力训练组（E）和耐力训练加氟他胺组（E+F）。使用氟他胺阻断大鼠体内的AR。R组和R+F组的大鼠进行3周的爬梯训练，负荷逐渐增加，而E组和E+F组的大鼠在跑步机上完成3周的中等强度有氧运动。检测大鼠的相对肌肉量（肌肉量/体重）。通过酶联免疫吸附测定法（ELISA）测定大鼠血清睾酮和IGF-1水平，通过实时聚合酶链反应（PCR）检测肌肉中IGF-1R和mTOR的mRNA水平。通过蛋白质免疫印迹法（Western blot）检测肌肉中AR、IGF-1、IGF-1R、mTOR、PI3K、Akt、p-PI3K和p-Akt的蛋白水平。
结果
（1）训练诱导的相对肌肉量增加和AR表达水平升高仅在R组大鼠的腓肠肌和E组大鼠的比目鱼肌中发现（选择性肌肉肥大），而氟他胺可阻断这种变化。（2）R组和E组大鼠的血清睾酮升高，氟他胺对此无影响。（3）IGF-1、IGF-1R和mTOR水平以及PI3K和Akt的活性在R组大鼠的腓肠肌和E组大鼠的比目鱼肌中选择性增强，而氟他胺可降低这些水平。AR在抗阻训练和耐力训练诱导的肌肉肥大中均发挥重要作用，这至少部分是通过IGF-1/IGF-1R-PI3K/Akt-mTOR途径介导的。
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