The Connection Between Androgen Receptors and Muscle Growth

Androgen Receptors and Muscle Growth: Insights from Recent Research (2024) Summary

Both males and females show increased total androgen receptor (AR) content after resistance exercise. Still, only males significantly increase nAR content, emphasizing the importance of AR localization in muscle growth.
Males exhibit a significant increase in nuclear-associated androgen receptor (nAR) content after muscle damage and after 10 weeks of resistance exercise training, which correlated with greater muscle hypertrophy.
Females do not show a significant increase in nAR content post-resistance exercise training, suggesting that AR-independent mechanisms drive muscle hypertrophy in females.

Introduction to Androgen Receptors

The relationship between androgen receptors and muscle growth has long been established, primarily through the role of testosterone.^1,2 Previous studies have indicate that androgen receptors play a role in resistance training muscle growth³, but there has been little new information on androgen receptors and resistance exercise in recent years. A recent study in the news “Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females” brings fresh new research on this topic. This study suggests that males experience a greater increase in androgen receptors after exercise, potentially explaining why males tend to gain more muscle than females.⁴

Review of the Literature on Androgen Receptors and Muscle Growth

Recently, the androgen receptor has emerges as a pivotal regulator of skeletal muscle in response to exercise. The current understanding of the impact of resistance exercise on female skeletal muscle involves examining the increase in endogenous androgens, such as testosterone and dihydrotestosterone (DHT), that it triggers, with the initial belief being that these androgens were the primary drivers of muscle hypertrophy.⁵

Androgen receptors are present in various tissues, including skeletal muscle, and are pivotal in mediating the effects of androgens on the body. Androgen receptors influence numerous physiological processes, including developing male characteristics, reproductive function, and muscle growth. When androgens bind to these receptors, they trigger a cascade of events that lead to protein synthesis and muscle hypertrophy.⁵ Upon activation by androgens, ARs translocate to the cell nucleus, where they bind to specific DNA sequences, regulating gene expression. This process enhances the synthesis of muscle proteins, contributing to increased muscle mass and strength.

Several factors can influence AR density in muscle tissues, including age, genetics, hormone levels, and training status.^1,6 Resistance training increases AR density, enhancing the muscle’s responsiveness to anabolic stimuli.. ⁷ Regular strength training can upregulate AR density in skeletal muscle, making it more receptive to androgens. There are notable differences in androgen receptor expression between males and females, which can affect the muscle growth response to resistance training. While males generally have higher levels of testosterone and androgen receptor expression, females can also experience significant muscle growth through resistance training, though the mechanisms may differ slightly.

Overview of the Study Protocol

The study aimed to investigate changes in androgen receptor content during muscle repair and characterize sex-based differences in AR-mediated responses following resistance training. The study involved 26 healthy young adults (13 males and 13 females), all recreationally active but not engaged in structured exercise for a year before the study. The participants were around 22 years old. Muscle biopsies to measure androgen content were taken at baseline, after a damaging exercise protocol, and following 10 weeks of RET.

Muscle Damage Eccentric Exercise Protocol: Participants performed 300 maximal eccentric contractions of the knee extensors to induce muscle damage.

Resistance Exercise Training: A 10-week full-body RET program consisting of four supervised weekly sessions, including various upper and lower body exercises (3-5 sets of 8-12 reps at 80% 1RM).

Results

Androgen Receptor Expression Post-Muscle Damage:

Males exhibit a significant increase in AR protein content 48 hours after muscle damage, while females do not.
There is an increase in total AR protein content in both sexes, but nAR content increases only in males.

Androgen Receptor Content Post-Resistance Training:

After 10 weeks of weight training, males show a higher increase in nAR content than females.
Both sexes had increase total AR content post-RET, but only males significantly increase nAR content.

Men Have Greater Androgen Receptor Responses After Resistance Training

The study provides new insights into how androgen receptors muscle growth interplay, particularly highlighting sex-based differences. The differential response in AR content between males and females is critical to this study. Males show a marked increase in nAR content after muscle damage and after RET, aligning with previous research indicating that AR activation is pivotal for muscle growth in males.³ This suggests that testosterone-induced AR activation is more pronounced in mediating muscle hypertrophy in males. Conversely, females did not show a significant increase in nAR content post-resistance exercise, implying that muscle hypertrophy or growth in females may be driven by other pathways, possibly involving estrogen receptors or other signaling molecules.

Implications for Training and Performance

The study’s results have practical implications for designing sex-specific training programs. Training protocols that enhance AR content, particularly nAR, could be more effective in maximizing muscle hypertrophy for males. This could involve higher intensities and volumes of resistance training, which have been shown to increase AR density and activity.⁸ For females, understanding the alternative pathways facilitating muscle growth is essential.

References

1 Mitchell, C. J. et al. Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy. Plos One 8, e78636 (2013). https://doi.org:10.1371/journal.pone.0078636

2 Lee, N. K. L. & MacLean, H. E. Polyamines, Androgens, and Skeletal Muscle Hypertrophy. Journal of Cellular Physiology 226, 1453-1460 (2011). https://doi.org:10.1002/jcp.22569

3 Morton, R. W. et al. Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men. Frontiers in Physiology 9 (2018). https://doi.org:10.3389/fphys.2018.01373

4 Hatt, A. A. et al. Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females. Faseb j 38, e23403 (2024). https://doi.org:10.1096/fj.202301291RR

5 Kraemer, W. J., Ratamess, N. A. & Nindl, B. C. Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise. J Appl Physiol (1985) 122, 549-558 (2017). https://doi.org:10.1152/japplphysiol.00599.2016

6 Sakai, H. & Imai, Y. Cell-Specific Functions of Androgen Receptor in Skeletal Muscles. Endocrine Journal 71, 437-445 (2024). https://doi.org:10.1507/endocrj.ej23-0691

7 Dubois, V. et al. A Satellite Cell‐specific Knockout of the Androgen Receptor Reveals Myostatin as a Direct Androgen Target in Skeletal Muscle. The Faseb Journal 28, 2979-2994 (2014). https://doi.org:10.1096/fj.14-249748

8 Sinha-Hikim, I., Roth, S. M., Lee, M. I. & Bhasin, S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab 285, E197-205 (2003). https://doi.org:10.1152/ajpendo.00370.2002