مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The role of the androgen receptor in endurance training-induced soleus muscle hypertrophy
The role of the androgen receptor in endurance training-induced soleus muscle hypertrophy
Ali Nosrati Andevari,1,*Ghasem Rasooli Moghadam,2Jouya Jalilpour,3Elahe Amini,4Durdi Qujeq,5
1. Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran 2. Islamic Azad University, Nour, Iran 3. Sport Pathology and Corrective Movements, Raja University, Qazvin, Iran. 4. Department of Paramedicine, Amol School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran 5. Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
Introduction: The androgen receptor (AR) is known as a key agent in regulating muscle responses to androgenic hormones such as testosterone and dihydrotestosterone. AR plays a crucial role in the processes of skeletal muscle growth, regeneration, and adaptation. Endurance activities upregulate AR in muscles. This receptor helps regulate metabolism, protein synthesis, and mitochondrial biogenesis by activating intracellular signaling pathways. The soleus muscle is composed mainly of slow-twitch (Type I) muscle fibers and plays a pivotal role in endurance activities such as long-distance running, cycling, and other aerobic sports due to its high oxidative capacity. The aim of this study was to investigate the role of the AR in endurance training-induced soleus muscle hypertrophy.
Methods: This review analyzed 40 original and review articles extracted from PubMed and Google Scholar databases using the keywords Androgen receptor, Endurance, Soleus, Hypertrophy, IGF-1, PI3K, Akt, mTOR, AMPK, and PGC-1α.
Results: The roles that AR plays in soleus muscle hypertrophy are through the involvement of IGF-1/IGF-1R, PI3K/Akt/mTOR, and PGC-1α pathways. AR acts as a transcription factor in the nucleus and upregulates IGF-1/IGF-1R. IGF-1, primarily produced by the liver and locally in skeletal muscle, interacts with IGF-1R, activating PI3K/Akt/mTORC1. This cascade agitate protein synthesis, hinders protein degradation, and elevates muscle hypertrophy. In the soleus muscle, IGF-1/IGF-1R signaling leads to upregulation of PGC-1α, which in turn enhances mitochondrial biogenesis and oxidative metabolism, which in part supports endurance adaptations. During endurance exercise, increased energy demand activates AMPK. AMPK can limit the anabolic effects of IGF-1 by inhibiting mTORC1. This antagonism in endurance training results in more limited hypertrophy in the soleus muscle than in resistance training. In the early stages of training, AMPK may hinder mTORC1 and limit hypertrophy. However, as training continues and energy status improves, AMPK's inhibition of mTORC1 attenuates. This allows IGF-1/IGF-1R to enhance protein synthesis and mild hypertrophy in the soleus muscle. This is because Akt can inactivate AMPK through phosphorylation at specific sites. Furthermore, IGF-1/IGF-1R and AMPK upregulate PGC-1α. This balance between AMPK and IGF-1/IGF-1R causes the soleus muscle to shift more toward metabolic adaptations (such as increased oxidative capacity) than toward notable hypertrophy during endurance exercise.
Conclusion: Endurance training upregulates AR in the soleus muscle and also leads to the activation of AMPK. AR agitates soleus muscle hypertrophy through activation of IGF-1/IGF-1R, PI3K/Akt/mTOR. However, through upregulation of PGC-1α, it elevates mitochondrial biogenesis and oxidative metabolism, thereby mitigating anabolism and hypertrophy. AMPK hinders hypertrophy and augments oxidative capacity through inhibition of mTORC1 activity and upregulation of PGC-1α. These results suggest that endurance training results in mild hypertrophy in soleus muscle due to AR activation.