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1 Department of Hand Surgery, Stockholm Soder Hospital, Karolinska Institutet, Stockholm, Sweden
2 Department of Biosciences, Karolinska Institutet, Stockholm, Sweden
3 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: hakan.westerblad{at}fyfa.ki.se.
Male skeletal muscles are generally faster and have a 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 (EDL, fast-twitch) muscles isolated from ER deficient (ER-/-) and wildtype mice of both sexes. The results showed generally shorter contraction and relaxation times in male as compared to 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 wildtype male muscles. In fact, female muscles and male ER-/- muscles displayed markedly better recovery than male wildtype muscles. Gene screening of male soleus muscles showed 25 genes that were differently expressed in ER-/- and wildtype mice. Five of these genes were selected for further analysis: Muscle Ankyrin Repeat Protein 2 (MARP2), Muscle LIM Protein (MLP), calsequestrin, parvalbumin, and aquaporin-1. The 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. The improved contractile performance of male ER-/- mouse muscles was associated with increased expression of mRNAs encoding important muscle proteins.
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