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Cited by 555Hormonal and reproductive studiesMuscle Physiology and DisordersAdipose Tissue and Metabolism

Androgens Stimulate Myogenic Differentiation and Inhibit Adipogenesis in C3H 10T1/2 Pluripotent Cells through an Androgen Receptor-Mediated Pathway

Singh, Rajan, Artaza, Jorge N., Taylor, Wayne E., Gonzalez-Cadavid, Nestor F., Bhasin, Shalender·2003·Endocrinology
DOI 10.1210/en.2003-0741
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Abstract

Testosterone supplementation increases skeletal muscle mass and decreases fat mass; however, the underlying mechanisms are unknown. We hypothesized that testosterone regulates body composition by promoting the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibiting their differentiation into adipogenic lineage. Mouse C3H 10T1/2 pluripotent cells were treated with testosterone (0-300 nM) or dihydrotestosterone (DHT, 0-30 nM) for 0-14 d, and myogenic conversion was evaluated by immunocytochemical staining for early (MyoD) and late (myosin heavy chain II; MHC) myogenic markers and by measurements of MyoD and MHC mRNA and protein. Adipogenic differentiation was assessed by adipocyte counting and by measurements of peroxisomal proliferator-activated receptor gamma 2 (PPAR gamma 2) mRNA and PPAR gamma 2 protein and CCAAT/enhancer binding protein alpha. The number of MyoD+ myogenic cells and MHC+ myotubes and MyoD and MHC mRNA and protein levels increased dose dependently in response to testosterone and DHT treatment. Both testosterone and DHT decreased the number of adipocytes and down-regulated the expression of PPAR gamma 2 mRNA and PPAR gamma 2 protein and CCAAT/enhancer binding protein alpha. Androgen receptor mRNA and protein levels were low at baseline but increased after testosterone or DHT treatment. The effects of testosterone and DHT on myogenesis and adipogenesis were blocked by bicalutamide. Therefore, testosterone and DHT regulate lineage determination in mesenchymal pluripotent cells by promoting their commitment to the myogenic lineage and inhibiting their differentiation into the adipogenic lineage through an androgen receptor-mediated pathway. The observation that differentiation of pluripotent cells is androgen dependent provides a unifying explanation for the reciprocal effects of androgens on muscle and fat mass in men.

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  • Testosterone exerts direct effects on adipose tissue by inhibiting adipogenic differentiation of mesenchymal stem cells, reducing lipid accumulation, and stimulating lipolysis through androgen receptor-mediated signalling.

    “In addition, testosterone exerts direct effects on adipose tissue by inhibiting the adipogenic differentiation of mesenchymal stem cells, reducing lipid accumulation, and stimulating lipolysis through androgen receptor-mediated signalling [186, 187].”

    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 [186]

  • This response may be through a testosterone-induced increase in the number of satellite cells and thus hypertrophy.

    “This response may be through a testosterone-induced increase in the number of satellite cells and thus hypertrophy (82, 83).”

    From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [82]

  • Testosterone inhibits the expression of the activity of lipoprotein lipase, the main enzymatic regulator of triglyceride uptake in the fat cell, preferentially in abdominal fat.

    “Testosterone inhibits the expression of the activity of lipoprotein lipase, the main enzymatic regulator of triglyceride uptake in the fat cell, preferentially in abdominal fat (28, 29).”

    From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [28]

  • TRT might decrease insulin resistance by promoting the commitment of pluripotent stem cells into the myogenic lineage and inhibiting their differentiation into mature adipocytes.

    “It is known that TRT might decrease IR by means of promoting the commitment of pluripotent stem cells into the myogenic lineage and inhibiting their differentiation into mature adipocyte (41).”

    From Effects of liraglutide on obesity-associated functional hypogonadism in men (2019) · cites this paper as [41]

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Authors
Singh, R., Artaza, J. N., Taylor, W. E., Gonzalez-Cadavid, N. F., & Bhasin, S.
Affiliations
Charles R. Drew University of Medicine and Science (US)
Corresponding author
Bhasin, Shalender
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2003-11
Volume
144
Issue
11
Pages
5081-5088
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2003-0741
OpenAlex
W2132485471
Cited by
555
References
35
Citations by year
2026: 6 · 2025: 19 · 2024: 26 · 2023: 18 · 2022: 28 · 2021: 21 · 2020: 29 · 2019: 20 · 2018: 23 · 2017: 25 · 2016: 24 · 2015: 28 · 2014: 31 · 2013: 28 · 2012: 23
FWCI
11.80
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5u54rr014616-10, 5u01dk054047-06)
  • National Institute on Aging (R01AG037193, SC1AG033407)
  • National Institute of Allergy and Infectious Diseases (1R01AIAG14369-01)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK-54047, R01DK049296, 2R01DK49296-02A, 1R01DK041748-01)
  • National Center for Research Resources (G12 RR 03026, P20RR11145, U54-RR14616, G12RR003026, P20RR011145)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD04178-01, 1R01HD042248-01)
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 › Adipose Tissue and Metabolism
Keywords
androgens, testosterone, dihydrotestosterone, androgen receptor, myogenesis, adipogenesis, C3H10T1/2 cells, MyoD, PPARγ2, C/EBPα, bicalutamide, muscle mass, fat mass, body composition, lineage determination
MeSH terms
Androgen Antagonists, Androgens, Anilides, Animals, Cell Differentiation, Cell Division, Cell Line, Mice, Inbred C3H, Nitriles, Receptors, Androgen, Dihydrotestosterone, Testosterone, Tosyl Compounds, Adipocytes, Muscle, Skeletal, Pluripotent Stem Cells, Mice

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