Cited by 318Hormonal and reproductive studiesMuscle Physiology and DisordersMuscle metabolism and nutrition

Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men

Sinha-Hikim, Indrani, Cornford, Marcia, Gaytan, Hilda, Lee, Martin L., Bhasin, Shalender·2006·The Journal of Clinical Endocrinology & Metabolism

Abstract

Objective: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. Participants: Healthy men, 60–75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. Methods: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. Results: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. Conclusions: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.

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Crossref · 10.1210/jc.2006-0357

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Authors
Sinha-Hikim, I., Cornford, M., Gaytan, H., Lee, M. L., & Bhasin, S.
Affiliations
  • Division of Endocrinology (I.S.-H., H.G., M.L.L., S.B.), Los Angeles, California 90059
  • University of California, Los Angeles (US)
  • Boston University (US)
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2006-08-01
Volume
91
Issue
8
Pages
3024-3033
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2098072804
Cited by
318
References
59
Citations by year
2026: 11 · 2025: 18 · 2024: 13 · 2023: 13 · 2022: 33 · 2021: 13 · 2020: 20 · 2019: 13 · 2018: 12 · 2017: 16 · 2016: 15 · 2015: 22 · 2014: 12 · 2013: 16 · 2012: 21
FWCI
7.47
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (1R01 AG-14369-01, R01AG014369)
  • National Institute of General Medical Sciences (S06GM068510)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049296, 2R01 DK49296-08, R01DK070534, R01DK059627, 1R01 DK 59627)
  • National Center for Research Resources (RR011145, P20RR011145)
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Keywords
testosterone supplementation, testosterone enanthate, skeletal muscle hypertrophy, satellite cells, muscle fiber cross-sectional area, older men, dose-response relationship, Notch signaling, myogenin, Numb, GnRH agonist, androgen deprivation therapy, vastus lateralis, community-dwelling older men
MeSH terms
Aged, Aging, Biopsy, Cell Count, Cell Division, Dose-Response Relationship, Drug, Humans, Hypertrophy, Immunohistochemistry, Male, Microscopy, Electron, Middle Aged, Testosterone, Myogenin, Muscle, Skeletal, Muscle Fibers, Skeletal, Microscopy, Confocal, Proliferating Cell Nuclear Antigen, Satellite Cells, Skeletal Muscle, Receptors, Notch

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