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Updated: Jul 17, 2026

Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration
Published on: June 7, 2012
Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice
Amy L Moran1, Steven A Nelson, Rachel M Landisch
1School of Kinesiology, University of Minnesota, Minneapolis, Minnesota 55455, USA. lowex017@umn.edu
Abstract:
Skeletal muscle contractility and myosin function decline following ovariectomy in mature female mice. In the present study we tested the hypothesis that estradiol replacement can reverse those declines. Four-month-old female C57BL/6 mice (n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated immediately with placebo or 17beta-estradiol (OVX + E(2)) while other mice were treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles were assessed in vitro for contractile function and susceptibility to eccentric contraction-induced injury. Myosin structural dynamics was analyzed in extensor digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy. Maximal isometric tetanic force was affected by estradiol status (P < 0.001) being approximately 10% less in soleus muscles from OVX compared with sham-operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX + E(2) mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during contraction was also affected (P = 0.045) and was approximately 15% lower in EDL muscles from OVX compared with OVX + E(2) mice [0.263 (SD 0.034) vs. 0.311 (SD 0.022)]. Plasma estradiol levels were correlated with maximal isometric tetanic force (r = 0.458; P < 0.001) and active stiffness (r = 0.329; P = 0.044), indicating that circulating estradiol influenced muscle and myosin function. Estradiol was not effective in protecting muscle against an acute eccentric contraction-induced injury (P >or= 0.401) but did restore ovariectomy-induced increases in muscle wet mass caused by fluid accumulation. Collectively, estradiol had a beneficial effect on female mouse skeletal muscle.
Insights
Estradiol replacement therapy effectively restored skeletal muscle strength and myosin function in ovariectomized mice. This hormone therapy reversed declines in muscle contractility and myosin binding, highlighting its beneficial effects on female muscle health.
Area of Science:
- Physiology
- Endocrinology
- Muscle Biology
Background:
- Ovariectomy (OVX) in mature female mice leads to declines in skeletal muscle contractility and myosin function.
- Estradiol, a key hormone, plays a crucial role in maintaining muscle health and function.
- Understanding the impact of estradiol replacement is vital for addressing age-related muscle decline in females.
Purpose of the Study:
- To investigate whether estradiol replacement can reverse ovariectomy-induced declines in skeletal muscle contractility and myosin function.
- To determine the effects of estradiol on muscle mass, injury susceptibility, and myosin binding dynamics post-ovariectomy.
Main Methods:
- Ovariectomy (OVX) or sham surgery was performed on mature female mice.
- Mice received either placebo or 17beta-estradiol (E2) treatment immediately or 30 days post-surgery.
- In vitro assessment of soleus muscle contractile function and ex vivo analysis of extensor digitorum longus (EDL) muscle myosin dynamics using electron paramagnetic resonance spectroscopy.
Main Results:
- Estradiol replacement restored maximal isometric tetanic force in soleus muscles of OVX mice, counteracting the approximate 10% decline observed in untreated OVX mice.
- The fraction of strong-binding myosin during contraction, reduced in OVX mice, was restored with estradiol treatment.
- Estradiol treatment normalized ovariectomy-induced increases in muscle wet mass due to fluid accumulation but did not protect against eccentric contraction-induced injury.
Conclusions:
- Estradiol replacement therapy effectively reverses ovariectomy-induced deficits in skeletal muscle contractility and myosin function in female mice.
- Circulating estradiol levels positively correlate with maximal isometric tetanic force and active muscle stiffness.
- Estradiol demonstrates a beneficial impact on skeletal muscle health in females, particularly concerning contractile properties and myosin dynamics.

