Hepcidin synthesis is directed by numerous elements apart from inflammation, including iron stores, hypoxia and erythropoiesis, and hepcidin release into the peripheral circulation is regulated by other proteins, including HJV, hereditary haemochromatosis protein,
transferrin receptor 2, matriptase-2 and neogenin.39,40 Pathologic modifications of hepcidin regulation are dominant in many disorders of iron metabolism, together with iron-loading anaemia, hereditary haemochromatosis, and anaemia of inflammation.2
The Tf complex ([Fe.sup.3+]/Tf) binds to the
transferrin receptor (TfR1) on the luminal membrane of endothelial cells and is subsequently internalized into endosomes where the acidic pH causes [Fe.sup.3+] to be released from the complex (TfR1/Tf/[Fe.sup.3+]).
Thus, the
transferrin receptor maintains cellular iron homeostasis (Levy et al., 1999).
Over-expression of
transferrin receptors on cancer cells makes them an attractive target for its suitable ligand to deliver anticancer drugs into target cells.
Caldron et al., "Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble
transferrin receptor and the sTfR/log ferritin index," American Journal of Hematology, vol.
de Sousa, "Transferrin and the
transferrin receptor: of magic bullets and other concerns," Inflammation and Allergy Drug Targets, vol.
Soluble
Transferrin Receptor (sTfR) and the sTfR-Ferritin Index.
Serum
transferrin receptor (STfR) concentrations were analyzed using a sandwich enzyme-linked immunosorbent assay (ELISA) at the Erhardt Laboratory in Germany, with iron deficiency defined as STfR > 8.3 mg/L [20, 21].
Hepcidin directly inhibits
transferrin receptor 1 expression in astrocytes via a cyclic AMP-protein kinase A pathway.
The lack of correlation with ferritin and TSAT suggests the need to examine the role of regulatory and functional markers of iron such as hepcidin [17-21] and other measures of iron stores, particularly soluble
transferrin receptor which has been shown to be a better marker of iron status than ferritin in Indigenous children [22].
Vezina, "Using soluble
transferrin receptor and taking inflammation into account when defining serum ferritin cutoffs improved the diagnosis of iron deficiency in a group of Canadian preschool Inuit children from Nunavik," Anemia, vol.
Indicators of the iron status of populations: free erythrocyte protoporphyrin and zinc protoporphyrin; serum and plasma iron, total iron binding capacity and transferrin saturation; and serum
transferrin receptor. Available at: http:// www.who.int/nutrition/publications/micronutrients/anaemia_iron_ deficiency/9789241596107_annex3.pdf.