Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice
Abstract
Androgens promote anabolism in skeletal muscle; however, effects on subsequent muscle function are less well defined because of a lack of reliable experimental models. We established a rigorous model of androgen withdrawal and administration in male mice and assessed androgen regulation of muscle mass, structure, and function. Adult C57Bl/6J male mice were orchidectomized (Orx) or sham-operated (Sham) and received 10 wk of continuous testosterone (T) or control treatment (C) via intraperitoneal implants. Mass, fiber cross-sectional area (CSA), and in vitro contractile function were assessed for fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles. After 10 wk, Orx+C mice had reduced body weight gain ( P < 0.05), seminal vesicle mass ( P < 0.01), and levator ani muscle mass ( P < 0.001) compared with Sham+C mice, and these effects were prevented with testosterone treatment. Orx+T mice had greater EDL ( P < 0.01) and SOL ( P < 0.01) muscle mass compared with Orx+C mice; however, median fiber CSA was not significantly altered in these muscles. EDL and SOL muscle force was greater in Sham+T compared with Orx+C mice ( P < 0.05) in proportion to muscle mass. Unexpectedly, Orx+T mice had increased fatigue resistance of SOL muscle compared with Orx+C mice ( P < 0.001). We used a rigorous model of androgen withdrawal and administration in male mice to demonstrate an essential role of androgens in the maintenance of muscle mass and force. In addition, we showed that testosterone treatment increases resistance to fatigue of slow- but not fast-twitch muscle.
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In mice, castration produces a decrease in body weight that is attenuated with testosterone supplementation.
“In mice, castration produces a decrease in body weight, which is attenuated with testosterone supplementation, and although overall muscle weight increases, the fiber CSA of the soleus and TA do not significantly change (6).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [6]
In mice, although overall muscle weight increases, the fiber CSA of the soleus and TA do not significantly change.
“In mice, castration produces a decrease in body weight, which is attenuated with testosterone supplementation, and although overall muscle weight increases, the fiber CSA of the soleus and TA do not significantly change (6).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [6]
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- Authors
- Axell, A.-M., MacLean, H. E., Plant, D. R., Harcourt, L. J., Davis, J. A., Jimenez, M., Handelsman, D. J., Lynch, G. S., & Zajac, J. D.
- Affiliations
- The University of Melbourne (AU)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2006-09
- Volume
- 291
- Issue
- 3
- Pages
- E506-E516
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2119647215
- Cited by
- 125
- References
- 73
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 11
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- testosterone, androgens, skeletal muscle atrophy, androgen withdrawal, orchiectomy, muscle fatigue resistance, muscle mass, muscle fiber cross-sectional area, slow-twitch muscle, fast-twitch muscle, extensor digitorum longus, soleus muscle, muscle force, male mice
- MeSH terms
- Animals, Body Weight, Male, Mice, Inbred C57BL, Muscle Contraction, Muscular Atrophy, Orchiectomy, Seminal Vesicles, Testis, Testosterone, Muscle, Skeletal, Muscle Fibers, Fast-Twitch, Muscle Fibers, Slow-Twitch, Muscle Fatigue, Mice
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