Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men

Abstract

The factors that underpin heterogeneity in muscle hypertrophy following resistance exercise training (RET) remain largely unknown. We examined circulating hormones, intramuscular hormones, and intramuscular hormone-related variables in resistance-trained men before and after 12 weeks of RET. Backward elimination and principal component regression evaluated the statistical significance of proposed circulating anabolic hormones (e.g., testosterone, free testosterone, dehydroepiandrosterone, dihydrotestosterone, insulin-like growth factor-1, free insulin-like growth factor-1, luteinizing hormone, and growth hormone) and RET-induced changes in muscle mass (n = 49). Immunoblots and immunoassays were used to evaluate intramuscular free testosterone levels, dihydrotestosterone levels, 5α-reductase expression, and androgen receptor content in the highest- (HIR; n = 10) and lowest- (LOR; n = 10) responders to the 12 weeks of RET. No hormone measured before exercise, after exercise, pre-intervention, or post-intervention was consistently significant or consistently selected in the final model for the change in: type 1 cross sectional area (CSA), type 2 CSA, or fat- and bone-free mass (LBM). Principal component analysis did not result in large dimension reduction and principal component regression was no more effective than unadjusted regression analyses. No hormone measured in the blood or muscle was different between HIR and LOR. The steroidogenic enzyme 5α-reductase increased following RET in the HIR (P < 0.01) but not the LOR (P = 0.32). Androgen receptor content was unchanged with RET but was higher at all times in HIR. Unlike intramuscular free testosterone, dihydrotestosterone, or 5α-reductase, there was a linear relationship between androgen receptor content and change in LBM (P < 0.01), type 1 CSA (P < 0.05), and type 2 CSA (P < 0.01) both pre- and post-intervention. These results indicate that intramuscular androgen receptor content, but neither circulating nor intramuscular hormones (or the enzymes regulating their intramuscular production), influence skeletal muscle hypertrophy following RET in previously trained young men.

Growth Hormone(s), Testosterone, Insulin-Like Growth Factors, and Cortisol: Roles and Integration for Cellular Development and Growth With Exercise

“…The increased DHT and FT were related to increased isokinetic strength, muscle CSA, and power (30). However, RT studies in younger men and women show no changes in muscle T or steroidogenic enzymes (17,31). However, responders to RT were shown to increase 5α-reductase (31).…”

“…However, RT studies in younger men and women show no changes in muscle T or steroidogenic enzymes (17,31). However, responders to RT were shown to increase 5α-reductase (31). It is possible that increased muscle steroidogenesis may be a mechanism to help counteract T reductions in older men undergoing RT but less likely in healthy, young men.…”

“…AR protein content is a critical variable in RT-induced androgenmediated skeletal muscle protein accretion in healthy men (31). The concentration of ARs in skeletal muscle depends on the muscle fiber type, sex, training status, and androgen concentrations.…”

Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway

“…But most of the reports about AR's role were focused on the sedentary participants. At training state, AR was likely to be very important not only for muscle hypertrophy but also strength promotion, for example, the submaximal running endurance and the maximum time to exhaustion were reduced in flutamide-treated rats [10] and in human, the intramuscular AR content influenced the cross-sectional areas of muscle in previously trained men [11]. Although muscle hypertrophy is a vital factor to enhance exercise performance, the roles of AR in exercise-induced muscle hypertrophy are not fully clarified, let alone the underlying molecular mechanisms.…”

“…On the contrary, global AR gene knockout (ARKO) and specific skeletal muscle tissue ARKO mice showed alterations in the muscle mass (such as gastrocnemius, quadriceps and soleus) [5,6], muscle glycogen [7] and exercise performance. 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. To our best knowledge, until now no ARKO model mice have been used to explore AR's role in exercise-induced changes in muscle mass and performance, moreover, ARKO mice could not be obtained commercially.…”