hepcidine

Hepcidin, sometimes spelled hepcidine, is a peptide hormone produced primarily by the liver. It is the central regulator of systemic iron homeostasis in humans and many vertebrates. The mature hormone is derived from a precursor encoded by the HAMP gene.

Hepcidin controls iron availability by binding to ferroportin, the only known cellular iron exporter located on the basolateral membranes of intestinal enterocytes, macrophages, and hepatocytes. Upon binding, ferroportin is internalized and degraded, reducing iron efflux into plasma and lowering serum iron and transferrin saturation.

Synthesis and regulation of hepcidin are tightly controlled by iron status, inflammation, and erythropoietic activity. The liver senses iron via the BMP/SMAD signaling pathway, with BMP6 playing a key role in upregulating hepcidin transcription. Inflammation induces hepcidin through interleukin-6 and the JAK/STAT3 pathway. Erythroferrone, produced during increased erythropoiesis, can suppress hepcidin to permit more iron availability. Hypoxia and heightened erythropoietic demand can also influence its levels, and renal function affects circulating concentrations.

Clinical relevance of hepcidin lies in its association with iron disorders. Elevated hepcidin contributes to anemia of inflammation and iron-refractory iron deficiency anemia, while in conditions such as hereditary hemochromatosis, hepcidin levels are inappropriately low. Serum hepcidin measurement is used mainly in research and to refine iron-status assessment. Therapeutically, strategies aim to modulate hepcidin signaling, using agonists to treat iron overload or antagonists to enhance iron availability in refractory anemia.