Regulators of hepcidin expression. Hepcidin is a common effector of 4 known regulators of iron homeostasis. Iron stores, erythropoietic demand, hypoxia, and inflammation all act by modulating hepatocyte production of hepcidin. Increased iron stores and inflammation both appear to increase hepcidin expression, primarily through signal transduction via the SMAD and JAK/STAT pathways, respectively. Increased/ineffective erythropoietic drive and hypoxia appear to decrease hepcidin expression, although the mechanisms of their control of hepcidin expression remain to be fully elucidated.