Estradiol and genistein antagonize the ovariectomy effects on skeletal muscle myosin heavy chain expression via ER-beta mediated pathways.

The age-related decline in ovarian sex hormone production following the onset of menopause alters skeletal muscle metabolic, structural and functional characteristics. The myosin heavy chain (MHC) expression pattern defines skeletal muscle contraction velocity and is therefore an important factor in skeletal muscle function. The present study was designed to examine the effects of 17beta estradiol (E2), estrogen receptor (ER) subtype selective agonists (ERalpha, ERbeta) or genistein (Gen) following ovary removal (OVX) in female Wistar rats in combination with a high intensity treadmill-based exercise protocol (Ex) or normal cage-based activity (NoEx) on MHC protein expression patterns in the slow fiber type m.Soleus (Sol) and the fast fiber type m.Gastrocnemius (Gas). Gen and E2 in the Sol significantly stimulated MHC-I expression relative to OVX only in the absence of exercise (NoEx). MHC-IIb expression in the Gas was significantly increased relative to OVX in Gen Ex and E2 Ex and NoEx groups. The estrogenic effects in the Sol and Gas were both predominantly mediated via ERbeta pathways, since the ERbeta agonist induced greater MHC increases than OVX or ERalpha. We therefore propose that high intensity exercise in combination with exposure to E2, Gen, ERalpha or ERbeta agonists in OVX rats exerts differential effects on MHC expression in skeletal muscles composed of mainly slow type I MHC (Sol) or fast type II MHC (Gas). In summary, the data shows that MHC composition is affected by estrogens and exercise in a fiber type specific manner and that these effects are mainly mediated by ER-beta. This is of great importance with respect to skeletal muscle health and potential treatment with ER selective agonists.