The DOI matches its Crossref record; 60 of the 62 references it cites were found in a registry or an index.
Sex-Related Differences in Gene Expression in Human Skeletal Muscle
Open accessAbstract
There is sexual dimorphism of skeletal muscle, the most obvious feature being the larger muscle mass of men. The molecular basis for this difference has not been clearly defined. To identify genes that might contribute to the relatively greater muscularity of men, we compared skeletal muscle gene expression profiles of 15 normal men and 15 normal women by using comprehensive oligonucleotide microarrays. Although there were sex-related differences in expression of several hundred genes, very few of the differentially expressed genes have functions that are obvious candidates for explaining the larger muscle mass of men. The men tended to have higher expression of genes encoding mitochondrial proteins, ribosomal proteins, and a few translation initiation factors. The women had >2-fold greater expression than the men (P<0.0001) of two genes that encode proteins in growth factor pathways known to be important in regulating muscle mass: growth factor receptor-bound 10 (GRB10) and activin A receptor IIB (ACVR2B). GRB10 encodes a protein that inhibits insulin-like growth factor-1 (IGF-1) signaling. ACVR2B encodes a myostatin receptor. Quantitative RT-PCR confirmed higher expression of GRB10 and ACVR2B genes in these women. In an independent microarray study of 10 men and 9 women with facioscapulohumeral dystrophy, women had higher expression of GRB10 (2.7-fold, P<0.001) and ACVR2B (1.7-fold, P<0.03). If these sex-related differences in mRNA expression lead to reduced IGF-1 activity and increased myostatin activity, they could contribute to the sex difference in muscle size.
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“Previous studies have identified over 3,000 genes that are differentially expressed in male and female skeletal muscle.”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [96]
In the citing paper
“Analysis of mRNA from both male and female vastus lateralis biopsies by microarray shows (when normalized to α-actinin) that the female muscle has 35% more MyHC-I/β, 30% less MyHC-IIa, and 15% less MyHC-IIx mRNA than the corresponding male muscle (96).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [96]
In the citing paper
“In this study, the authors focus on two particular genes that are upregulated in women compared with men and that are known to code for proteins that are in signaling pathways of growth factors known to regulate muscle mass: growth factor receptor-bound protein 10 (GRB10) and activin receptor type-2A (ACVR2A).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [96]
In the citing paper
“The identification of over 3,000 genes differentially regulated in male and female muscle highlights the complex differences that occur in skeletal muscle from both sexes (96).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [96]
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“Myostatin has a major role in determining muscle size. Constitutive myostatin knockout in mice leads to a hypermuscular phenotype caused by an increased number of fibers and fiber enlargement”
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“It is well accepted that IGF-1 has an anabolic effect on muscle [28].”
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Items 201–224 of 224
Sex differences in kinematics and quadriceps activity for fast isokinetic knee extension
Jeon, J., Lee, D.-Y., Yu, J.-H., Kim, J., Kim, S.-G., & Hong, J. (2023) · Isokinetics and Exercise Science · doi:10.3233/ies-220050
“Using Significance Analysis of Microarrays program, Welle et al. [15] re-ported that there were more than 3,000 sex-related differences between male and female skeletal muscles.”
Gillen, Z. M. (2024) · International Journal of Strength and Conditioning · doi:10.47206/ijsc.v4i1.252
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Takikawa, M., Ohminami, H., Uchida, T., Kitamura, A., Adachi, Y., Mori, Y., Ohnishi, K., Masuda, M., Yamanaka-Okumura, H., & Taketani, Y. (2025) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.24-229
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“Additionally, human studies have shown increased mRNA of the activin receptor IIB (AcvRIIB) gene in women compared to men (39), which could account for increased myostatin activity in females and negative regulation of skeletal muscle size.”
Sex Differences in the EXerCise Introduction to Enhance Performance in Dialysis Trial
Mallamaci, F., Bratsiakou, A., D’Arrigo, G., Tripepi, G., Lamberti, N., Torino, C., Manfredini, F., & Zoccali, C. (2025) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.0000000759
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“…stem from variation in genetics, anatomy and hormonal profiles between sexes (Fu et al., 2009; Janse de Jonge, 2003; McNulty et al., 2020; Welle et al., 2008), which directly influence physiological systems including the circulatory, respiratory, nervous, and muscular systems (Ansdell et…”
de Araújo, A. A., Dias, D. D. S., Alves, A. N., Bernardes, N., Curi, R., Damaceno‐Rodrigues, N. R., Caldini, E. T. E. G., Ferreira‐Mesquita, R. A., Irigoyen, M. C., & Angelis, K. D. (2025) · Physiological Reports · doi:10.14814/phy2.70516
“Additionally, we note that numerous genes are regulated differently in the skeletal muscles of men and women, which can affect musculoskeletal structure (Welle et al., 2008).”
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“[ 18, 19] This research focuses on the calcaneal BMD of female university students aged 19–25 at Southern Medical University.”
Biomechanical and physiological differences between males and females in endurance running
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“By 4 months, dietary effects fade and OA pools likely reflect flux (desaturation, β -oxidation/lipophagy and partitioning into membranes vs. storage) modulated by sex-specific muscle physiology (e.g., enzyme programmes and substrate use) [41].”
Dabbs, N. C., Binkley, H. M., Bott, C., Fragala, M. R., Herda, A. A., Moeskops, S., Moore, E. W. G., Smith‐Ryan, A. E., & Triplett, N. T. (2026) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000005493
Metadata
- Authors
- Welle, S., Tawil, R., & Thornton, C. A.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Welle, Stephen
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-01-02
- Volume
- 3
- Issue
- 1
- Pages
- e1385
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2148100
- OpenAlex
- W2094746410
- Cited by
- 224
- References
- 62
- Citations by year
- 2026: 8 · 2025: 22 · 2024: 19 · 2023: 27 · 2022: 24 · 2021: 23 · 2020: 9 · 2019: 12 · 2018: 16 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 4
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Rochester
- National Institutes of Health
- National Institute on Aging (AG18254, AG17891, P30AG018254, R01AG017891)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR/NS48143, K24AR048143)
- National Center for Research Resources (RR-00044, M01RR000044)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- sex differences, skeletal muscle, gene expression, sexual dimorphism, muscle mass, Grb10, ACVR2B, IGF-1 signaling, facioscapulohumeral muscular dystrophy, mitochondrial proteins, ribosomal proteins, growth factor pathways
- MeSH terms
- Adult, Aged, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Sex Factors, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis
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