Model of the inhibition of hepcidin production by BMP6. Increased EPO expression leads to an expansion of erythroid precursors, which secrete ERFE, a hormone that circulates in the blood and that blocks the binding of BMPs 5, 6, and 7 to their BMP receptors. The decrease in BMP signaling in the liver leads to lower hepcidin production. Hepcidin negatively regulates the efflux of iron into the blood by downregulation of ferroportin. The lower hepcidin levels increase iron-bound Tf in the blood to promote the iron uptake of erythropoietic precursors to satisfy their needs for heme synthesis. BMPRs, BMP receptors; Fe-Tf, iron-loaded transferrin.