Cited by 224Muscle Physiology and DisordersGenetics and Physical PerformanceMuscle metabolism and nutrition

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

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Abstract

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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Crossref · 10.1371/journal.pone.0001385

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Figures

Figure 1 Volcano plot illustrating statistical significance of sex-related differences (shown as negative log of the ANOVA P level, so that the most significant differences are on top) in relation to magnitude of mean differences (shown as log of the female/male expression ratio, so that genes expressed at higher levels in women have positive values and those expressed at higher levels in men have negative values). The lower panel is a magnified version of part of the upper panel, excluding the very large differences for Y-chromosome genes and XIST, which are enclosed in red boxes in the upper panel. The three solid red circles in the lower panel represent the probe sets for the GRB10 gene transcript.
Figure 1 Volcano plot illustrating statistical significance of sex-related differences (shown as negative log of the ANOVA P level, so that the most significant differences are on top) in relation to magnitude of mean differences (shown as log of the female/male expression ratio, so that genes expressed at higher levels in women have positive values and those expressed at higher levels in men have negative values). The lower panel is a magnified version of part of the upper panel, excluding the very large differences for Y-chromosome genes and XIST, which are enclosed in red boxes in the upper panel. The three solid red circles in the lower panel represent the probe sets for the GRB10 gene transcript.CC BY · PubMed Central
Figure 2 Summary of functional categories of genes expressed at higher levels in men than in women (nominal P<0.01). The percentage of genes expressed at a higher level in men that were assigned to the functional categories (rectangular boxes) was higher than would be expected by chance based on the percentage of all genes in these categories (Bonferroni P<0.05 according to EASE program). The ovals show the numbers of genes in more specific functional categories, with arrows showing how they relate to the broader categories.
Figure 2 Summary of functional categories of genes expressed at higher levels in men than in women (nominal P<0.01). The percentage of genes expressed at a higher level in men that were assigned to the functional categories (rectangular boxes) was higher than would be expected by chance based on the percentage of all genes in these categories (Bonferroni P<0.05 according to EASE program). The ovals show the numbers of genes in more specific functional categories, with arrows showing how they relate to the broader categories.CC BY · PubMed Central

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Metadata

Authors
Welle, S., Tawil, R., & Thornton, C. A.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Welle, Stephen
Venue
PLoS ONE
Published
2008-01-02
Volume
3
Issue
1
Pages
e1385
ISSN
1932-6203 (ISSN-L)
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
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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