Abstract
BackgroundAndrogen 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?MethodsForty-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. Conclusions: 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.
Highlights
Testosterone is widely reported to affect muscle mass and exercise capacity, with high level testosterone promoting, YIN et al Nutrition & Metabolism (2020) 17:26 prostatic hyperplasia) resulted from long-term or large dose of androgen administration, androgen supplementation is strictly limited [2], and selective androgen receptor modulators (SARMs) especially the non-steroidal tissuespecific SARMs were used currently to activate Androgen receptor (AR) in specific tissue
Flutamide reversed the training-induced selective muscle hypertrophy Compared with control, the relative muscle mass of gastrocnemius but not soleus was increased in R rats (Fig. 2a), while enhanced muscle mass was observed
Flutamide reversed the training-induced selective increase of AR protein level in muscles instead of promotion of testosterone in serum The serum levels of testosterone in R and E rats were significantly increased compared to control, and blocked AR by flutamide did not change the levels of serum testosterone in the training rats, while flutamide elevated serum testosterone of the untrained control rats (Fig. 3)
Summary
Testosterone is widely reported to affect muscle mass and exercise capacity, with high level testosterone promoting, YIN et al Nutrition & Metabolism (2020) 17:26 prostatic hyperplasia) resulted from long-term or large dose of androgen administration, androgen supplementation is strictly limited [2], and selective androgen receptor modulators (SARMs) especially the non-steroidal tissuespecific SARMs were used currently to activate AR in specific tissue. The important role of AR in the increases of muscle mass and exercise performance at untrained state was demonstrated [5, 8,9,10,11], but whether AR exerted crucial role in exercise-induced muscle hypertrophy in vivo have not been thoroughly verified. Until now no ARKO model mice have been used to explore AR’s role in exercise-induced changes in muscle mass and performance, ARKO mice could not be obtained commercially. 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. 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?
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