Sex-related differences in gene expression in human skeletal muscle

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PLoS ONE. 2008 Jan 2;3(1):e1385.

Sex-related differences in gene expression in human skeletal muscle.

Welle S, Tawil R, Thornton CA.

Department of Medicine, University of Rochester, Rochester, New

York, United States of America.

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.