One gastrocnemius muscle was stored in RNALater according to the manufacturers instructions. The other gastrocnemius was snap frozen in LN2 and stored at �C 80uC for protein analysis. It has recently become appreciated that the autophagy-lysosome system plays a fundamental role in the process of muscle atrophy. We therefore investigated in expression of the autophagy genes BCL-2/adenovirus E1B-19kDA-interacting protein 3, and GABA receptor-associated protein like 1 along with the lysosomal protease Cathepsin L, which are regulated transcriptionally and consistently elevated in muscle undergoing atrophy. AG-013736 VEGFR/PDGFR inhibitor chemotherapy significantly induced Bnip3 and Gabapl1 GRLox/Lox mice. However, this GDC-0199 response was partially blocked in mGRKO mice, where the induction of Bnip3 by chemotherapy was significantly attenuated. We also assessed the conversion of light chain 3 B -I to LC3B-II, a process involving lipidation that is required for formation of autophagic vesicles. Consistent with prior work, mice treated with LPS demonstrate a significant increase in the 14 kD LC3B-II isoform. However, chemotherapy failed to induce a significant conversion of LC3B-I to LC3B-II in either genotype of mice, consistent with the relatively weak induction of autophagy genes relative to LPS treatment. Skeletal muscle is also a known producer of inflammatory cytokines. Therefore, we investigated whether chemotherapy administration increases muscle cytokine production and whether this effect is dependent on glucocorticoid signaling. In response to chemotherapy administration, there was a significant induction of IL-1b in the muscle of mGRKO but not in GRLox/Lox mice consistent with the role of glucocorticoids as a negative regulator of inflammation. Chemotherapy failed to induce IL-6 or TNF expression in the muscle of either genotype of mouse. Collectively, these data demonstrate that glucocorticoids are required for the induction of the catabolic program in response to chemotherapy administration.The most pronounced changes occur in genes regulating proteasomal degradation of skeletal muscle, while the effects on other pathways such as the autophagy lysosome system are relatively modest compared with other catabolic stimuli.