Abstract
Estradiol (E&sub2;) deficiency decreases muscle strength and wheel running in female mice. It is not known if the muscle weakness results directly from the loss of E&sub2; or indirectly from mice becoming relatively inactive with presumably diminished muscle activity. The first aim of this study was to determine if cage activities of ovariectomized mice with and without E&sub2; treatment differ. Ovariectomized mice were 19-46% less active than E&sub2;-replaced mice in terms of ambulation, jumping, and time spent being active (P ≤ 0.033). After E&sub2;-deficient mice were found to have low cage activities, the second aim was to determine if E&sub2; is beneficial to muscle contractility, independent of physical activities by the mouse or its hindlimb muscles. Adult, female mice were ovariectomized or sham-operated and randomized to receive E&sub2; or placebo and then subjected to conditions that should maintain physical and muscle activity at a constant low level. After 2 wk of hindlimb suspension or unilateral tibial nerve transection, muscle contractile function was assessed. Soleus muscles of hindlimb-suspended ovariectomized mice generated 31% lower normalized (relative to muscle contractile protein content) maximal isometric force than suspended mice with intact ovaries (P ≤ 0.049). Irrespective of whether the soleus muscle was innervated, muscles from ovariectomized mice generated ∼20% lower absolute and normalized maximal isometric forces, as well as power, than E&sub2;-replaced mice (P ≤ 0.004). In conclusion, E&sub2; affects muscle force generation, even when muscle activity is equalized.