Conclusion
Our results demonstrate a role for 17ß-estradiol for the prevention of skeletal muscle mass loss in female tumor bearing mice. Furthermore, 17ß-estradiol prevented cachexia's disruption in skeletal muscle signaling involving AMPK and mTORC1, in addition to improving mitochondrial function in female tumor bearing mice.
Methods
Female C57BL/6 (B6; N = 82) and Apc Min/+ (MIN; N = 88) mice were used in two separate experiments. In experiment 1, mice were sacrificed at either 12 (N = 20) or 20 (N = 41) weeks of age. Body weight and estrous cycle presence was determined weekly. In experiment 2, B6 and MIN mice were randomly allocated to: Control (N = 17), received E2 pellet (E2, N = 18), ovariectomy surgery (OVX; N = 19) or ovariectomy surgery with E2 pellet (OVX + E2; N = 21). 17ß-estradiol was administered through an implanted slow-releasing pellet (0.1 mg). In estrogen and ovariectomy experiments, food intake, and functional outcomes were recorded 1 week prior to sacrifice.
Results
We report that E2 administration prevented body weight loss, muscle mass loss, cage inactivity, and grip strength loss associated with cachexia. In skeletal muscle, E2 reduced skeletal muscle AMPK phosphorylation, improved mTORC1 signaling, and prevented mitochondrial dysfunction.