Transferrin receptor activity and localisation in the rat duodenum

It is not known how the efficiency of intestinal iron absorption is regulat ed. One hypothesis suggests that an interaction between the transferrin rec eptor (TfR) and the haemochromatosis protein (HFE) regulates the level of i ron loading in crypt cells. The hypothesis goes on to suggest that this det ermines the amount of transport protein, expressed in villus enterocytes, t hat is involved in iron absorption. Mice with haploinsufficiency for TfR ar e iron deficient and this is thought to be caused by reduced iron absorptio n. This suggests that TFR may play a role in the regulation and/or mechanis m of iron absorption. We investigated TfR function and distribution by meas uring iron uptake from plasma transferrin and by immunohistochemistry. The uptake of transferrin-bound iron (Tf-Fe-2) into mucosal cells subsequently separated along the crypt-villus axis was compared to the presence of TfR, determined by immunohistochemistry using frozen and wax sections. Frozen se ctions showed TfR staining in crypt and villus epithelial cells. In wax sec tions TfR was only identified in a supranuclear region commencing in entero cytes at the crypt-villus junction and attaining greatest levels at the vil lus tip. This indicates that the processing of wax tissue exposes a TfR epi tope that otherwise remains undetectable when studied in frozen sections. T his appearance in paraffin sections was inversely related to the uptake of Tf-Fe-2. Supranuclear TfR was not associated with lysosomes, since there wa s no difference in the uptake of normal Tf-Fe-2 and that of the non-digesti ble cellobiose Tf-Fe-2, and Western blot analysis revealed similar amounts of TfR in crypt and villus cells. Also the uptake of Tf-Fe-2 increased line arly with time, albeit less in villus than crypt cells, suggesting that mat uration of an efflux system in villus cells is not responsible for this dif ference. We hypothesise that TfR in the supranuclear region of villus enter ocytes may play a role in iron absorption.