Effect of Estrogen on Skeletal Muscle Anabolic Signaling in the Apc Min/+ Mouse

Skeletal muscle homeostasis involves the balance of skeletal muscle protein synthesis to degradation. Stimuli such as nutrition, insulin, and hormones regulate skeletal muscle anabolic signaling through the mTORC1 signaling axis and is dysregulated with disease. Cancer-induced cachexia is defined as unintentional muscle mass loss. The ApcMin/+ mouse is a model of cancer-induced cachexia and exhibits suppressed mTORC1 signaling. Previous have shown differential responses in cachexia’s progression in the female Min mouse and could be attributed to ovarian function. Purpose: The purpose of this study is to examine the role of long-term estrogen on skeletal muscle anabolic signaling in the female Min mouse. Methods: B6 and ApcMin/+ mice were randomly allocated to SHAM or E2 treatments at 11 weeks. Mice were sacrificed at 18 weeks of age after a 5 hour fast and gastrocnemius muscle was used for protein analysis. Results: Body weight decreased in the ApcMin/+ mouse, however Estrogen preserved body weight loss in the ApcMin/+ mouse. Similarly, gastrocnemius weight decreased in the ApcMin/+ mouse, and estrogen preserved muscle loss. Estrogen increased uterine weight in both mice. Estrogen suppressed ribosomal protein S6 activation while activation of eukaryotic elongation factor binding protein 1 was increased in the B6 mouse. In the ApcMin/+ mouse estrogen increased rpS6 and 4EBP1 activation. Conclusion: Long term estrogen rescued muscle mass in the female ApcMin/+ mouse. While long term estrogen suppressed anabolic signaling in the B6 mouse, estrogen improved anabolic signaling. Estrogen may be a potential therapeutic treatment for females when ovarian function is suppressed