Effects of dietary iron loading with carbonyl iron and of iron depletion on intestinal growth, morphology, and expression of transferrin receptor in the rat.

The intestine has one of the highest cell turnovers of the body, which is characterised by cell proliferation and differentiation occurring at specified locations along the crypt to the villus axis. These processes require iron for the synthesis of iron-dependent proteins, the supply of which is mediated through the transferrin receptor. In this study, we varied dietary iron intake to determine whether this affected the pattern of transferrin receptor expression and activity on intestinal cell turnover and cell differentiation. Variations in iron stores were produced by feeding a control diet and diets high (2% carbonyl iron) or low in iron for 8-10 weeks. Total tissue DNA and the incorporation of thymidine into DNA, and RNA and protein were used as indices of hyperplasia and hypertrophy, respectively. Transferrin receptor expression and activity in the intestinal mucosa were assessed by using in situ hybridisation and the uptake of transferrin-bound 55Fe. Iron loading caused mucosal hypertrophy in the small and large intestines. With all levels of dietary iron transferrin- receptor expression and activity were present within the progenitor and differentiating regions of the mucosa but ceased upon cellular maturation. Feeding carbonyl iron leads to mucosal hypertrophy. Expression of transferrin receptor mRNA and activity is dependent upon proliferation and differentiation of the mucosal epithelium, regardless of the cellular iron stores within these cells.