Estradiol's beneficial effect on murine muscle function is independent of muscle activity.
Estradiol (E₂) deficiency decreases muscle strength and wheel running in female mice. It is not known if the muscle weakness results directly from the loss of E₂ 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 E₂ treatment differ. Ovariectomized mice were 19-46% less active than E₂-replaced mice in terms of ambulation, jumping, and time spent being active (P ≤ 0.033). After E₂-deficient mice were found to have low cage activities, the second aim was to determine if E₂ 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 E₂ 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 E₂-replaced mice (P ≤ 0.004). In conclusion, E₂ affects muscle force generation, even when muscle activity is equalized.
Program in Physical Medicine and Rehabilitation Sciences, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Sarah M
SM
Greising
Kristen A
KA
Baltgalvis
Allison M
AM
Kosir
Amy L
AL
Moran
Gordon L
GL
Warren
Dawn A
DA
Lowe
D000818:Animals; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy
D004958:Estradiol