Model of Tf-dependent regulation of hepcidin expression. Tf-dependent regulation of hepcidin expression occurs via two axes in hpx mice. In the erythroid-regulator axis, Tf delivers iron to the erythron, leading to effective erythropoiesis; with effective erythropoiesis comes decreased activity of the erythroid-regulator and decreased inhibition of hepcidin expression. In the stores-regulator axis, Tf leads to stimulation of hepcidin expression in a process requiring hemochromatosis genes such as Bmp6, Hfe, Hjv and Tfr2. Treatment of hpx mice with exogenous Tf leads to effective erythropoiesis and decreased erythroid-regulator activity via the erythroid-regulator axis and stimulation of hepcidin expression via the stores-regulator axis. Treatment of hpx mice with wild-type RBCs leads to decreased erythroid-regulator activity without the need for endogenous erythropoiesis. Treatment of hpx mice with doxorubicin then Tf leads to stimulation of hepcidin expression via the stores-regulator axis.