TRANSFERRIN RECEPTOR DISTRIBUTION AND IRON DEPOSITION IN THE HEPATIC LOBULE OF IRON-OVERLOADED RATS

Under the condition of obvious iron-overload, there is a zonal hemosiderin (iron) deposition in hepatic lobules. The deposition is heaviest in the periportal (zone 1) and lightest in the perivenous (zone 3) hepatocytes. However, the mechanism for this pattern of iron deposition is obscure. Hepatic tissues from control, iron-deficient or iron-overloaded Wistar rats were used to study its pathogenesis, Iron-deficiency was induced by a low iron regimen, Iron-overload was produced by repeated intraperitoneal injections of ferric nitrilotriacetate (Fe3+-NTA) for 1-4 months. Liver tissues of the rats were immunohistochemically and histochemically stained for transferrin receptor (TfR), transferrin (Tf), ferritin (Ft), and iron. The staining intensity of TfR, Tf and Pt increased in hepatocytes of iron-deficient rats and decreased in that of the iron-overloaded in comparison with the control rats. TfR staining was strong in zone 1, with gradual transition into weak staining in zone 3 hepatocytes of the rat liver. TfR located primarily on the hepatocyte membrane. Tf had both membranous and cytoplasmic distribution. Many hepatocytes in group B had strong cytoplasmic Tf staining. Conversely, only a few hepatocytes had weakly stained cytoplasmic Tf in group C. Hepatocytes and Kupffer cells were Ft positive in control rats, Ft was distributed only in the cytoplasm. The staining intensity of Ft was stronger in zone 3 than in zone 1 hepatocytes of iron-deficient rats. In iron-overloaded rats, the iron deposition was severe in zone 1 and mild in zone 3 hepatocytes. These findings suggest that uptake of iron into hepatocytes in vivo is regulated and mediated by TfR and Tf. Gradient TfR distribution from zone 1 to 3 hepatocytes and active TfR-Tf mediated iron uptake resulted in the zonal iron deposition in the hepatic lobule of iran-overloaded rats.