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Difference in skeletal muscle function in males vs. females: role of estrogen receptor-

¹Department of Hand Surgery, Stockholm Söder Hospital, SE-118 83 Stockholm; and Departments of ²Biosciences and ³Physiology and Pharmacology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Submitted 1 March 2004 ; accepted in final form 22 July 2004

Male skeletal muscles are generally faster and have higher maximum power output than female muscles. Conversely, during repeated contractions, female muscles are generally more fatigue resistant and recover faster. We studied the role of estrogen receptor- (ER) in this gender difference by comparing contractile function of soleus (mainly slow-twitch) and extensor digitorum longus (fast-twitch) muscles isolated from ER-deficient (ER^–/–) and wild-type mice of both sexes. Results showed generally shorter contraction and relaxation times in male compared with female muscles, and ER deficiency had no effect on this. Fatigue (induced by repeated tetanic contractions) and recovery of female muscles were not affected by ER deficiency. However, male ER^–/– muscles were slightly more fatigue resistant and produced higher forces during the recovery period than wild-type male muscles. In fact, female muscles and male ER^–/– muscles displayed markedly better recovery than male wild-type muscles. Gene screening of male soleus muscles showed 25 genes that were differently expressed in ER^–/– and wild-type mice. Five of these genes were selected for further analysis: muscle ankyrin repeat protein-2, muscle LIM protein, calsequestrin, parvalbumin, and aquaporin-1. Expression of these genes showed a similar general pattern: increased expression in male and decreased expression in female ER^–/– muscles. In conclusion, ER deficiency results in increased performance during fatigue and recovery of male muscles, whereas female muscles are not affected. Improved contractile performance of male ER^–/– mouse muscles was associated with increased expression of mRNAs encoding important muscle proteins.

skeletal muscle fatigue; gender differences; muscle LIM protein; muscle ankyrin repeat protein

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