Effects Of Androgen Receptor On The Promotion Of Exercise Performance Of Rats Induced By Resistance And Endurance Trainings And Its Mechanism

Object: Androgens promote the protein synthesis of skeletal muscles and increase the muscle mass and strength by binding to androgen receptor(AR).However,the mechanisms of AR on muscles mass and strength are still unclear.The purpose of the study was to detect the effect of AR on the performance of rats with endurance and resistance trainings using AR inhibitor-Flutamine sustained-release pellet and its possible mechanisms-the role of insulin-like growth factor 1(IGF-1)/ phosphatidylinositol 3 kinase(PI3K)/ protein kinase B(Akt)/ mammalian target of rapamycin(mTOR)pathway.Methods: After adaptive exercise,48 of eight-week old male SD rats were randomly divided into 6 groups of 8 rats each: control group(C),AR inhibitor Flutamide group(F),resistance training group(R),resistance training + Flutamide group(R+F),endurance exercise group(E)and endurance exercise + Flutamide group(E+F).The rats of F,R+F and E+F groups were implanted subcutaneously a Flutamide sustained-release pellet to inhibit AR before experiments.The rats of E and E+F groups participated in 3-week moderate intensity aerobic exercise on a treadmill at a speed of 20 m/min for 60 min(once a day and 6 days/week),and R and R+F groups rats underwent 3-week resistance training with gradually increasing intensity,six times a week.At 36 h after the last training,the body weight,the strength(including the maximum grip force and the maximum load at starting movement)and endurance(time of exhaustive exercise)of all the rats were determined.The samples of blood,gastrocnemius and soleus of the rats were collected at 36 h after the experiments.The serum level of IGF-1 and the content of muscle glycogen in gastrocnemius and soleus were determined by ELISA and anthrone method,respectively.The mRNA levels of IGF-1R and mTOR and the protein levels of IGF-1,IGF-1R,PI3 K,p-PI3 K,Akt,p-Akt,mTOR,MHC,fs-myosin and ss-TnT in gastrocnemius and soleus of the rats were determined by real time PCR and Western blot,respectively.Results:1.The increased body weights of control and resistance training rats were mediated by AR,while the decreased body weight of endurance training rats was irrelevant to AR.Flutamide inhibited the increases of the body weight in control group rats over time(p<0.01)and in resistance group rats induced by resistance training(p<0.05),while had no effect on the decreased weight of endurance training rats.2.The up-regulations of the maximum force and speed strength by resistance training were mediated by AR,while the up-regulated endurance by endurance training was not associated with AR.Resistance training significantly increased the relative grip force of rats(p<0.05),which was reversed by Flutamide(p<0.05).Endurance training promoted the endurance of rats(p<0.05),which was not influenced by Flutamine.3.The increased relative weight of gastrocnemius by resistance training and of soleus by endurance training were mediated by AR.Resistance training increased the relative weight of intermediate muscle gastrocnemius(p<0.05)and exerted no role on the weight of slow muscle soleus,and the resistance exercise-induced increase of gastrocnemius weight was reversed by Flutamide(p<0.01).Endurance training only increased the relative weight of soleus(p<0.05),which was also reversed by Flutamide(p<0.01).4.The increased fast twitch fibers of gastrocnemius by resistance training was mediated by AR,while the increased slow twitch fibers of soleus by endurance training was not related to AR.Resistance training increased the content of fs-myosin,a specific protein of fast twitch fibers,in gastrocnemius(p<0.05)and had no effect on the content of ssTnT,a specific protein of slow twitch fibers in gastrocnemius.Furthermore,the effect of resistance training on fs-myosin in gastrocnemius was reversed by Flutamide(p<0.01).Endurance training increased the content of ssTnT(p<0.05)rather than fs-myosin in soleus,but the effect of endurance training on ssTnT in soleus was not changed by Flutamide.5.The increased expressions of MHC in gastrocnemius by resistance training and in soleus by endurance training were mediated by AR.Resistance training and endurance training increased the protein levels of MHC in gastrocnemius(p<0.05)and soleus(p<0.05),respectively.Flutamide inhibited the increase of MHC in gastrocnemius by resistance training and in soleus by endurance training(both p<0.01).6.The increased muscle glycogen in gastrocnemius and soleus by resistance and endurance trainings were mediated by AR.Compared with control group,the muscle glycogen in gastrocnemius were increased by resistance(p<0.01)and endurance(p<0.05)trainings,and similar increases of muscle glycogen in soleus were also found by resistance(p<0.05)and endurance(p<0.01)trainings.Furthermore,the increased muscle glycogen in gastrocnemius and soleus by resistance and endurance trainings were decreased by Flutamide(both p<0.01).7.The increased levels of IGF-1,IGF-1R and mTOR in gastrocnemius by resistance training and in soleus by endurance training were mediated by AR,while no change of serum IGF-1 by the two trainings.Resistance training and endurance training significantly increased the mRNA levels of IGF-1R and mTOR in gastrocnemius(p<0.05)and soleus(p<0.05),respectively.And the effects of resistance and endurance trainings on IGF-1R and mTOR were reversed by Flutamide(both p<0.01).At protein levels,the increased protein levels of IGF-1,IGF-1R and mTOR in gastrocnemius induced by resistance training were decreased by Flutamide(p<0.05,p<0.01,and p<0.01,respectively);and the increased protein levels of IGF-1 and IGF-1R in soleus resulted from endurance training were also reversed by Flutamide(p<0.05,and p<0.01,respectively).In addition,although there was no change in the serum levels of IGF-1 by resistance and endurance trainings and in the protein level of mTOR in soleus by endurance training,the above indicators were decreased by Flutamide.8.The increased activities of PI3 K and Akt in gastrocnemius by resistance training and in soleus by endurance training were mediated by AR.The activities of PI3 K and Akt,reflected by the ratio of p-PI3K/PI3 K and p-Akt/Akt,were increased in gastrocnemius by resistance training and in soleus by endurance training(both p<0.05).Furthermore,the two trainings-induced increases of PI3 K and Akt activities in muscles were reversed by Flutamide(both p<0.05).Conclusion:1.The increases of maximum force and speed strength by resistance training were through the mediation of AR,while the enhanced endurance by endurance training was not associated with AR.2.The mechanisms by which resistance training enhanced the strength of rats via AR were related to the increases of the relative weight,fast twitch fibers,intrinsic contractility and muscle glycogen content in gastrocnemius.3.Endurance training-induced enhancements of the relative weight,fast twitch fibers and muscle glycogen content in soleus were mediated by AR,but the increase of soleus contractility was irrelevant to AR,which might be explain why the endurance kept unchanged in endurance training rats after blocking AR.4.The activated AR induced by resistance and endurance trainings activated IGF-1/IGF-1R-PI3K/Akt-mTOR signaling pathway,thus increasing the relative weight of gastrocnemius in resistance training rats and of soleus in endurance training rats.However,the mechanism by which the activated AR enhanced the fast switch fibers,MHC protein levels and muscle glycogen content of muscles needs to be studied.