Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle

► Testosterone loss suppresses myofibrillar protein synthesis and Akt/mTORC1 signaling. ► Testosterone loss activates muscle FoxO3a and its transcriptional targets. ► Androgen administration restores Akt/mTORC1/FoxO3a signaling in castrated mice. ► In C2C12 myotubes, testosterone can activate mTORC1 independent of Akt activation. ► 24 h T withdrawal amplifies the activation of Akt/mTORC1 after acute T stimulation.