Cachexia is a debilitating condition that occurs with chronic disease including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; interleukin-6 (IL-6) signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and the progression of cancer cachexia in the female ApcMin/+ mouse. Ovarian reproductive function was monitored in female ApcMin/+ mice. Disease-related cessation of estrous cycling (acyclicity) was seen in 38% of mice. Acyclicity was associated with severe cachexia including morphological and functional losses and enhanced muscle inflammatory gene expression. Interestingly, ovariectomy rescued body weight, muscle mass and function, but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproduction function and cachexia progression in female ApcMin/+ mice.
- Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism