Coincident increase in periportal expression of iron proteins in the iron-loaded rat liver

Background: The liver is the major iron storage organ in the body and, as a result, total body iron stores closely regulate hepatocyte iron uptake, st orage and release. Transferrin, transferrin receptor and ferritin facilitat e these processes. Methods: Expression of the three proteins was localized by immunohistochemi stry and in situ hybridization on normal, iron-loaded and iron-deficient ra t livers. Gel shift assays were used to determine iron regulatory protein ( IRP) binding activity. Results: In the normal rat liver, all three proteins and mRNA were evenly d istributed throughout the hepatic lobule. In iron-loaded liver, increased i ron stores were found in a periportal distribution, coinciding with increas ed periportal protein levels of each protein. Periportal transferrin and fe rritin mRNA levels were also increased. Hepatic transferrin and transferrin receptor expression was increased in iron deficiency compared with control s; however, despite no change in ferritin mRNA levels being found, ferritin protein was not detected. Hepatic IRP2 binding activity was decreased in i ron loading and increased in iron deficiency. Conclusion: The combined findings of this study were that, in the dietary i ron-loaded rat model, increased iron stores were localized to periportal he patocytes and that these same hepatocytes also had increased ferritin, tran sferrin receptor and transferrin protein expression. This response suggests that additional, non-IRP control mechanisms may be involved in the regulat ion or stability of these proteins. In iron deficiency the inverse post-tra nscriptional regulation of ferritin and transferrin receptor was consistent with IRP regulation. (C) 1999 Blackwell Science Asia Pty Ltd.