Hepcidin

Hepcidin is a recently discovered peptide hormone produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals.^[1]

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The peptide that would later become known as hepcidin was first reported as LEAP-1, for Liver-Expressed Antimicrobial Protein ^[2]. Independently, in a search for antimicrobial peptides, researchers working in the lab of Tomas Ganz discovered a peptide associated with inflammation, and named it "hepcidin" after observing that it was produced in the liver ("hep-") and appeared to have bacteriocidal properties ("-cidin" for "killing")^[3]. Both groups were focused on the antimicrobial properties of the peptide. HAMP is the gene that encodes for hepcidin.

Soon after this discovery, researchers discovered that hepcidin production in mice increased in conditions of iron overload as well as in inflammation. Genetically modified mice engineered to overexpress hepcidin died shortly after birth with severe iron deficiency, again suggesting a central and not redundant role in iron regulation. The first evidence that linked hepcidin to the clinical condition known as the anemia of inflammation came from the lab of Nancy Andrews in Boston when researchers looked at tissue from two patients with liver tumors with a severe microcytic anemia that did not respond to iron supplementation. The tumor tissue appeared to be overproducing hepcidin, and contained large quantities of hepcidin mRNA. Removing the tumors surgically cured the anemia.

Taken together, these discoveries suggested that hepcidin regulated the release of iron in the body.

More recent discoveries have shown that hepcidin directly interacts with ferroportin, a protein that transports iron out of cells that store it. This is another confirmation that hepcidin is directly involved in iron homeostasis. Furthermore, several mutations in hepcidin have been found that result in juvenile hemochromatosis. The majority of juvenile hemochromatosis cases are due to mutations in hemojuvelin, a regulator of hepcidin production.

Hepcidin has shown fairly consistent activity against fungi. Hepcidin's antibacterial activity currently seems to be inconsistent. The current scientific evidence suggests that hepcidin is a central regulatory hormone and its main action is to regulate systemic iron homeostasis.

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