Effect of testosterone on muscle mass and muscle protein synthesis
Abstract
We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1–13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.
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Testosterone binds to androgen receptors in skeletal muscle, activating anabolic pathways such as mTORC1 and promoting protein synthesis.
“Another example is testosterone, which binds to androgen receptors in skeletal muscle, activating anabolic pathways such as mTORC1 and promoting protein synthesis [184, 185].”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [184]
On average, men have over 30% more skeletal muscle mass than women, primarily due to the anabolic and anti-catabolic effects of testosterone.
“On average, men have over 30% more skeletal muscle mass than women [ 56 ], primarily due to the anabolic and anti-catabolic effects of testosterone, which promotes muscle protein synthesis and reduces degradation [ 57 – 61 ].”
From Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications (2026) · cites this paper as [57]
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Sex differences in potassium regulation: evidence, molecular mechanisms and clinical implications
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- Authors
- Griggs, R. C., Kingston, W., Jozefowicz, R. F., Herr, B. E., Forbes, G., & Halliday, D.
- Affiliations
- University of Rochester Medicine (US)
- Department of Neurology, University of Rochester School of Medicine and Dentistry, New York 14642.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1989-01-01
- Volume
- 66
- Issue
- 1
- Pages
- 498-503
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2118523099
- Cited by
- 517
- References
- 27
- Citations by year
- 2026: 15 · 2025: 28 · 2024: 22 · 2023: 19 · 2022: 15 · 2021: 14 · 2020: 34 · 2019: 13 · 2018: 23 · 2017: 10 · 2016: 13 · 2015: 17 · 2014: 9 · 2013: 12 · 2012: 17
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-22099)
- National Center for Research Resources (RR-00044)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- testosterone enanthate, muscle mass, muscle protein synthesis, whole-body protein synthesis, leucine oxidation, total body potassium, creatinine excretion, muscle fiber diameter, anabolic steroids, muscle morphometry
- MeSH terms
- Adult, Body Weight, Creatinine, Humans, Leucine, Male, Muscle Proteins, Muscles, Organ Size, Oxidation-Reduction, Potassium, Testosterone
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