Ferritin gene expression and transferrin receptor activity in intestine of rats with varying iron stores

Expression of transferrin receptor and ferritin genes has been shown previously to be under transcriptional and posttranscriptional regulation, the latter being reciprocally regulated according to cellular iron levels. This study examined transferrin receptor function and ferritin gene expression along the crypt-villus axis of the intestinal tract in rats with varying iron stores. Altered iron stores were produced by feeding a control diet and diets low or high in iron (2% carbonyl iron) for 8-10 wk. Expression and activity of the ferritin genes were assessed by in situ hybridization and immunohistochemical localization, respectively. Transferrin receptor activity was determined by the uptake of intravenously injected transferrin-bound iron and was shown to increase with the level of iron loading. In all iron status groups, ferritin mRNA was seen at highest levels in the epithelial cells of the crypt and macrophages within the lamina propria and at lower levels in villus epithelial cells. In all groups, ferritin protein was not seen in the crypt region but was seen with increasing staining in the apical two-thirds of the villus cells of control and iron-loaded, but not iron-deficient, rats. Ferritin staining increased with iron loading. We conclude that in undifferentiated crypt cells ferritin genes are transcribed, but the message is not translated. After differentiation, these genes appear to be controlled posttranscriptionally by cellular iron stores.