Hepcidin--the iron regulatory hormone.

Abstract

The existence of an iron regulatory hormone was postulated primarily to account for the observed interactions between the anatomically distinct sites of iron absorption, recycling and utilisation. Hepcidin is now acknowledged to be the main iron regulatory hormone. It is a 25-amino acid peptide exclusively synthesized by the liver, initially identified as part of a search for novel antimicrobial peptides.1 There was no indication that it had an additional role in iron metabolism until 2001, when mouse studies were published showing that hepatic hepcidin mRNA synthesis was induced by iron loading.2 Hepcidin was first isolated from human urine and named on the basis of its site of synthesis (hep-) and its in-vitro antibacterial properties (-cidin). In human urine, the predominant form contains 25 amino acids, although shorter 22 and 20 amino acid peptides are also present. The main peptide is notable for containing eight cysteine residues linked as four disulphide bridges resulting in a molecule with a simple hairpin structure and the bridges in a ladder-like configuration. This structure is characteristic of peptides capable of disrupting bacterial membranes and is similar to other antimicrobial peptides. This article will briefly summarise recent work identifying hepcidin as a key player in iron metabolism and its role as an iron regulatory hormone. More detailed information is presented in a review article by Ganz.3 More of the manifold functions of hepcidin are being regularly discovered, and it will be some time before the complete repertoire of functions of this versatile peptide are established.