CELLULAR EXPRESSION AND REGULATION OF IRON TRANSPORT AND STORAGE PROTEINS IN GENETIC HEMOCHROMATOSIS

Genetic haemochromatosis is a common iron overload disorder of unknown aetiology. To characterize the defect of iron metabolism responsible for this disease, this study localized and semi-quantified the mRNA an d protein expression of transferrin, transferrin receptor and ferritin in the Liver and duodenum of patients with genetic haemochromatosis. Biopsies were obtained from iron-loaded non-cirrhotic patients with ge netic haemochromatotic and control patients with normal iron stores. A dditional duodenal biopsies were obtained from patients with iron defi ciency. Immunohistochemical and in situ hybridization analysis for tra nsferrin, transferrin receptor and ferritin was performed. Hepatic tra nsferrin, transferrin receptor and ferritin protein expression was loc alized predominantly to hepatocytes and was increased in patients with genetic haemochromatosis when compared with normal controls. Interest ingly, hepatic ferritin mRNA expression was not increased in these sam e patients. In the genetic haemochromatotic duodenum, ferritin mRNA an d protein was localized mainly to crypt and villus epithelial cells an d the level of expression was decreased compared with normal controls, but similar to iron deficiency;. Duodenal transferrin receptor mRNA a nd protein levels colocalized to epithelial cells of the crypt and vil lus were similar to normal controls. Early in the course of genetic ha emochromatosis and before the onset of hepatic fibrosis, transferrin r eceptor-mediated iron uptake by hepatocytes contributes to hepatic iro n overload. Increased hepatic ferritin expression suggests this is the major iron storage protein. While persisting duodenal transferrin rec eptor expression may be a normal response to increased body iron store s in patients with genetic haemochromatosis, decreased duodenal ferrit in levels suggest that duodenal mucosa is regulated as if the patient were iron deficient.