Hepcidin: An emerging hormone in iron homeostasis: A review

Abstract

Hepcidin, is a peptide hormone, which is a key regulator of systemic iron homeostasis and its unbalanced production contributes to iron disorders is derived from liver. Hepcidin was discovered by Krause and coworkers in the year 2000. The name ‘Hepcidin’ was given, from the place of synthesis in liver hepatocytes (hep-) and its antimicrobial activity (-cidin). The gene encoding hepcidin is expressed in various organs like liver, heart, lungs, brain, spinal cord, intestine, stomach, pancreas, adipocytes, skeletal muscles, testis and macrophages. Hepcidin is a 25 amino acid peptide hormone which inhibits entry of iron into the plasma compartment from the three main sources of iron: dietary absorption in the duodenum, the release of recycled iron from macrophages and the release of stored iron from hepatocytes. This blocking of iron flow is achieved by Hepcidin functios by causing degradation of iron receptor, via an iron transporter ferroportin. Hepcidin production is tightly regulated by (1) increased plasma and liver iron as a feedback mechanism to maintain stable body iron levels, (2) decreased by erythroid activity to ensure iron supply for erythropoiesis and (3) increased by inflammation as a host defense mechanism to limit extracellular iron availability to microbes. Hepcidin levels reflect the integration of signals involved in iron regulation and it directly controls iron absorption and bioavailability in circulation. Its measurement is a useful clinical tool for the management of iron disorders in the body. Recent evidence shows that the deficiency of hepcidin may cause iron overloading even in the much milder common form of hemochromatosis, from mutations in the HFE gene. The discovery of hepcidin and its role in iron metabolism could lead to new therapies for hemochromatosis and anemia of inflammation.