Iron proteins of duodenal enterocytes isolated from mice with genetically and experimentally altered iron metabolism

The molecular basis for the control of iron absorption by the duodenum rema ins unknown: however, ferritin (Ft) and the iron status of enterocytes have been suggested as regulatory factors. We determined the iron and Ft status of duodenal enterocytes from mice with hypotransferrinaemia, a genetic def ect leading to greatly enhanced iron absorption, and for comparison we also investigated mice with experimentally-altered iron absorption. Duodenal en terocytes were isolated and analysed for Ft and non-haem iron content and f or transferrin binding (as a measure of transferrin receptor activity). RNA was extracted from the duodenal mucosa and examined for transferrin recept or and H- and L-Ft mRNA levels by Northern hybridization analysis. Ft level s were elevated in enterocytes of hypotransferrinaemic mice, similar to tha t seen in iron dextran-injected mice of the CD1-strain. Enterocyte Ft level s were reduced in mice fed a diet diminished in iron, but unchanged in hypo xic mice enterocytes. Enterocytes of hypotransferrinaemic mice had normal n on-haem iron levels and transferrin binding; however, enterocytes from CD-1 mice fed a low iron diet had increased transferrin binding and a decreased non-haem iron content, Duodenal mRNA levels for transferrin receptor and H -Ft were unchanged in hypotransferrinaemic mice, whereas L-Ft was increased . We conclude from the Ft and non-haem iron contents and transferrin bindin g that duodenal enterocytes from hypotransferrinaemic mice are not simply i ron deficient, leading to increased expression of iron carriers proteins, D uodenal iron absorption can be enhanced in mice even when enterocyte Ft lev els are raised or unchanged, suggesting that iron absorption is regulated b y developmentally programmed expression of iron transporters by enterocytes .