Despite its abundance in the environment,
iron is poorly bioavailable and subject to strict conservation and internal recycling by most organisms. In vertebrates, the stability of
iron concentration in plasma and extracellular fluid, and the total body
iron content are maintained by the interaction of the
iron-regulatory
peptide hormone hepcidin with its receptor and cellular
iron exporter
ferroportin (SLC40a1).
Ferroportin exports
iron from duodenal enterocytes that absorb
dietary iron, from
iron-recycling macrophages in the spleen and the liver, and from
iron-storing hepatocytes.
Hepcidin blocks
iron export through
ferroportin, causing hypoferremia. During
iron deficiency or after
hemorrhage,
hepcidin decreases to allow
iron delivery to plasma through
ferroportin, thus promoting compensatory erythropoiesis. As a host defense mediator,
hepcidin increases in response to
infection and
inflammation, blocking
iron delivery through
ferroportin to blood plasma, thus limiting
iron availability to invading microbes.
Genetic diseases that decrease
hepcidin synthesis or disrupt
hepcidin binding to
ferroportin cause the
iron overload disorder hereditary
hemochromatosis. The opposite phenotype,
iron restriction or
iron deficiency, can result from genetic or inflammatory overproduction of
hepcidin.