FIGURE 1:

Systemic iron regulation. Iron is absorbed by the duodenum where it is released into the circulation via the iron exporter ferroportin to be loaded onto transferrin (Tf). The majority of iron is utilized by red blood cells (RBCs) for the synthesis of the hemoglobin, requiring ∼25 mg of iron per day. The daily requirements for intestinal iron uptake are only 1–2 mg per day due to efficient recycling of iron from RBCs. Iron recycling is performed primarily by reticuloendothelial macrophages which phagocytize senescent RBCs and then export iron via ferroportin back into the circulating pool of Tf-bound iron. Excess iron is also stored within hepatocytes. Hepcidin regulates systemic iron balance by inducing ferroportin degradation to inhibit iron absorption from the duodenum and iron release from macrophage and hepatocyte stores. Hepcidin production in the liver is stimulated by iron and inflammation to limit iron availability, while hepcidin production is inhibited by iron deficiency, anemia and hypoxia to increase iron availability. Several other growth factors and steroid hormones have recently been demonstrated to suppress hepcidin expression in the liver, including EGF, HGF, testosterone and estrogen.