Building Muscle: How Exercise & Hormones Work Together (Testosterone, Estrogen, GH, IGF-1)

Our muscles rely on a delicate balance of protein buildup and breakdown. Exercise, especially weight training, helps build muscle by boosting protein synthesis. Hormones like testosterone (men) and estrogen (women) play key roles in muscle growth and adaptation. Testosterone directly promotes muscle protein building, while estrogen influences it indirectly. Growth hormone and its downstream factor, IGF-1, work together to indirectly build muscle. According to a review published by the journal Frontiers in Physiology , understanding these hormones and their interplay with exercise is crucial for maintaining muscle mass and function throughout life, especially with sex-specific responses and age-related changes.

Key Points

This review highlights the importance of muscle protein synthesis (MPS) and breakdown (MPB) in maintaining skeletal muscle mass, which is crucial for various bodily functions throughout life. Several factors, including exercise, aging, and disease can influence this balance.

Physical activity:

• Resistance exercise (RE) is particularly effective in stimulating muscle hypertrophy by enhancing MPS.

Hormonal influences:

• Testosterone is a key anabolic hormone that promotes muscle growth and adaptation to exercise. Its effects on muscle protein turnover contribute to maintaining muscle mass.

• Estrogen, although less dominant, plays a role in muscle function and adaptation in women, especially during the menstrual cycle and menopause.

• Growth hormone (GH) indirectly stimulates muscle growth by triggering the production of insulin-like growth factor (IGF-1), which has potent anabolic effects.

• IGF-1, influenced by exercise and GH, has direct anabolic effects on muscle, promoting hypertrophy and strength.

Key takeaways:

• The interplay between hormones, exercise, and dietary factors is crucial for optimal muscle health.

• Sex-specific responses to exercise and age-related declines in hormones require further research for personalized strategies.

• Understanding the metabolic and molecular effects of hormones on muscle can guide interventions for promoting muscle growth, repair, and adaptation.

• Hormonal regulation plays a significant role in maintaining muscle mass and function, impacting overall health and well-being throughout life.

Understanding Skeletal Muscle Mass Regulation

Following a phase of rapid growth during early life, skeletal muscle mass stabilizes in adulthood, governed by a delicate equilibrium between muscle protein synthesis (MPS) and breakdown (MPB). This balance, however, can be perturbed by various stimuli, including exercise, aging, or disease. Notably, resistance exercise (RE) stands out as a potent intervention for promoting muscle hypertrophy, primarily by augmenting MPS. Despite extensive research into pharmacological strategies for combating muscle wasting, RE remains the gold standard for preserving and enhancing skeletal muscle mass.

The Role of Hormones in Muscle Adaptation

Testosterone emerges as a central player in the adaptive responses of skeletal muscle to exercise training. As a primary anabolic hormone, testosterone interacts with androgen receptors (AR) within muscle tissue, initiating a cascade of molecular events conducive to muscle hypertrophy. Notably, testosterone not only influences muscle structure and metabolism but also enhances bone density and neural function, underscoring its multifaceted role in human physiology.

Insights into Testosterone Physiology

Testosterone, synthesized primarily in Leydig cells in men and, to a lesser extent, in women's ovaries and adrenal glands, exerts its effects via binding to AR. Upon binding, testosterone modulates gene expression, leading to alterations in skeletal muscle structure and function. Additionally, testosterone can undergo conversion to dihydrotestosterone (DHT), a more potent androgen, further enhancing its anabolic actions. Evidence from exogenous testosterone administration, gonadotropin-releasing hormone analogues, and AR antagonists underscores the indispensability of testosterone in mediating muscle growth and strength gains.

Implications for Muscle Protein Turnover

Beyond its direct effects on muscle structure, testosterone influences muscle protein turnover, orchestrating a delicate balance between synthesis and breakdown. By promoting anabolism and inhibiting catabolism, testosterone fosters net muscle accretion, a process vital for maintaining skeletal muscle mass throughout the life course. Moreover, fluctuations in other hormones such as GH and IGF-1, coupled with dietary factors, further modulate muscle protein turnover, highlighting the intricate interplay between hormonal signaling and metabolic regulation.

Estrogen's Role in Women's Adaptation to Exercise

While testosterone predominates in male physiology, estrogen assumes significance in women's adaptive responses to exercise. Influenced by the menstrual cycle and menopausal transition, estrogen modulates muscle function and adaptation, albeit to a lesser extent compared to testosterone. Understanding the interplay between estrogen and exercise-induced muscle adaptation holds profound implications for promoting women's health and well-being across the lifespan.

The Dynamics of Testosterone Response to Resistance Exercise

Following a bout of RE, young men experience acute transient elevations in testosterone levels, believed to be pivotal in driving hormonal adaptations linked with muscle growth. This surge in serum testosterone is accompanied by an upregulation of androgen receptor (AR) mRNA and protein content within the muscle. Mechanistically, high-intensity RE stimulates the release of luteinizing hormone (LH) from the anterior pituitary, which in turn regulates testosterone secretion from Leydig cells in the testes.

Understanding the Transient Nature of Testosterone Response

It's crucial to note that the acute testosterone response to RE is transient, returning to baseline rapidly post-exercise. However, the upregulation of AR mRNA and protein content can persist for up to 1–2 days post-RE, enhancing testosterone uptake into the muscle and potentiating its anabolic effects over longer periods.

Correlating Testosterone Elevations with Muscle Strength and Hypertrophy

While some studies have suggested correlations between RE-induced testosterone elevations and muscle strength and hypertrophy, discrepancies exist due to various factors such as timing of sampling and exercise protocols. For instance, RE loads of less than 70% of one-repetition maximum (1-RM), upper body-focused exercises, and longer rest periods between repetitions may not stimulate significant post-exercise testosterone responses despite observed increases in muscle protein synthesis (MPS) and anabolic signaling.

Unraveling the Role of Testosterone in Exercise-induced Muscle Adaptation

Studies comparing high vs. low hormone environments have yielded conflicting results regarding the role of testosterone in exercise-induced muscle adaptation. Some indicate minimal influence, while others suggest potentiation of muscle strength gains. This underscores the complexity of hormonal regulation in muscle physiology and the need for further research to elucidate the precise mechanisms at play.

Testosterone's Role in Women's Adaptive Processes

In the context of sex-specific responses to exercise, testosterone's role in women's adaptive processes remains contentious. Although women experience increases in testosterone following RE in some studies, the effects on muscle growth are uncertain. Moreover, with aging, there's a gradual decline in bioavailable circulating testosterone in both men and women, potentially contributing to age-related deficits in muscle responsiveness to exercise training. The decline in testosterone levels with age parallels the decline in muscle mass, underscoring the potential significance of testosterone in preserving muscle health during aging.

Metabolic and Molecular Effects of Testosterone in Skeletal Muscle

The anabolic effects of testosterone and AR upregulation post-RE involve both genomic and non-genomic pathways. RE increases AR mRNA transcription via specific signaling pathways, while testosterone enhances AR mRNA translation and stabilizes AR protein content within the muscle. The activation of androgen-response elements (AREs) by testosterone-bound AR stimulates the transcription of protein targets, including insulin-like growth factor-1 (IGF-1), which plays a crucial role in muscle protein accretion. Additionally, testosterone independently activates intracellular signaling pathways such as Akt/mTOR/S6K1 and ERK1/2, contributing to cellular growth and hypertrophy.

Estrogen in Skeletal Muscle:

• Estrogen, primarily produced in the ovaries, plays a role in regulating skeletal muscle metabolism and function.

• Estrogen is important for muscle regrowth, which is mediated by estrogen receptors within skeletal muscle tissue.

• Exercise, especially resistance exercise (RE), acutely increases estrogen levels by augmenting the activity of the aromatase enzyme.

• Acute estrogen release post-RE may reduce exercise-induced muscle damage and improve recovery.

• Estrogen activates pathways like insulin/IGF-1 and PI3K/Akt, enhancing muscle protein synthesis (MPS) and muscle growth.

• Decreased estrogen levels in post-menopausal women may contribute to sarcopenia, and estrogen replacement has been shown to attenuate age-related muscle mass decline.

Growth Hormone (GH) in Muscle Metabolism:

• GH, secreted by the anterior pituitary, is released in response to RE and is involved in muscle repair and growth.

• RE induces acute increases in GH levels, which peak at the end of exercise and return to baseline within 60 minutes.

• GH acts indirectly by stimulating the hepatic generation of IGF-1, which triggers anabolic pathways promoting muscle maintenance and growth.

• GH binds to its receptor, leading to the activation of pathways like JAK2/STAT5, IRS1/Akt, and MAPK, contributing to muscle hypertrophy.

Insulin-like Growth Factor 1 (IGF-1) in Muscle Metabolism:

• IGF-1, released from the liver in response to GH, promotes muscle growth and repair.

• Exercise-induced increases in systemic IGF-1 levels contribute to muscle hypertrophy, neurogenesis, and improved muscle strength.

• GH-induced IGF-1 release from the liver maintains or increases IGF-1 secretion despite negative feedback loops.

• Local production of IGF-1 in muscle, independent of circulating levels, plays a crucial role in muscle growth and adaptation to exercise.

Conclusion:

• Exercise-induced changes in steroid and peptide hormone responses, including estrogen, GH, and IGF-1, are essential for muscle adaptation and growth.

• The anabolic effects of hormones like GH and IGF-1 act indirectly via the stimulation of anabolic signaling pathways.

• Hormonal patterns differ between sexes, impacting muscle adaptation to exercise. Further research is needed to understand these mechanisms better.

Overall, the text highlights the intricate role of hormones in mediating the metabolic and molecular responses of skeletal muscle to exercise, with implications for muscle growth, repair, and adaptation.

Reference Article

Gharahdaghi, N., Phillips, B. E., Szewczyk, N. J., Smith, K., Wilkinson, D. J., & Atherton, P. J. (2021). Links Between Testosterone, Oestrogen, and the Growth Hormone/Insulin-Like Growth Factor Axis and Resistance Exercise Muscle Adaptations. Frontiers in physiology, 11, 621226. https://doi.org/10.3389/fphys.2020.621226

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Disclaimer

The information provided in this article is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment. Never disregard professional medical advice or delay in seeking it because of something you have read in this article.