Estradiol treatment, physical activity, and muscle function in mice that have experienced natural or chemically‐induced ovarian failure

Abstract

Estradiol (E2) treatment in young adult ovariectomized mice reverses deleterious effects on muscle and also increases physical activity. The aim of this project was to determine if similar effects occur with E2 treatment in mice with intact but failed ovaries. Wheel running and daily cage activities were monitored for ~55 days before mice were euthanized and soleus muscles analyzed for contractility. Aged, 24-mo-old, ovarian-failed mice that were treated with E2 wheel ran 2-fold less than aged-matched untreated mice (p=0.03), with no differences in cage activities such as ambulation distance and jump counts (p≥0.55) or in soleus muscle maximal isometric force (p≥0.39). Because E2 treatment did not improve muscle function or physical activity in the aged, ovarian-failed mice as predicted, a second study was initiated. 3-mo-old mice were treated with 4-vinylcyclohexene diepoxide (VCD) to cause premature senescence of the ovaries, resulting in young, ovarian-failed mice. VCD-treated mice wheel ran and engaged in cage activities to the same extent as control and VCD+E2 mice (P≥0.18), indicating that the presence of the ovaries is important for physical activity whether or not ovarian hormones are being produced. Further analysis of skeletal muscle contractility following VCD treatment may begin to explain the effects of aging and E2 on muscle function. Supported by NIH grant R01-AG031743.