DMT1 and FPN1 expression during infancy: developmental regulation of iron absorption

Abstract

.-Two iron transporters, divalent metal transporter1 (DMT1) and ferroportin1 (FPN1) have been identified; however, their role during infancy is unknown. We investigated DMT1, FPN1, ferritin, and transferrin receptor expression, iron absorption and tissue iron in iron-deficient rat pups, iron-deficient rat pups given iron supplements, and controls during early (day 10) and late infancy (day 20). With iron deficiency, DMT1 was unchanged and FPN1 was decreased (Ϫ80%) at day 10. Body iron uptake, mucosal iron retention, and total iron absorption were unchanged. At day 20, DMT1 increased fourfold and FPN1 increased eightfold in the low-Fe group compared with controls. Body iron uptake and total iron absorption were increased, and mucosal iron retention was decreased with iron deficiency. Iron supplementation normalized expression levels of the transporters, body iron uptake, mucosal iron retention, and total iron absorption of the low-Fe group to those of controls at day 20. In summary, the molecular mechanisms regulating iron absorption during early infancy differ from late infancy when they are similar to adult animals, indicating developmental regulation of iron absorption.

Iron absorption by Belgrade rat pups during lactation

“…However, the mechanisms responsible for the acquisition of iron from milk by the developing rat duodenum, as well as the function of DMT1 in the rat neonatal duodenum, are unclear. Previous reports (20) and observations made in this study (Figs. 3 and 4) show that in the rat intestine DMT1 is present at very low levels at birth but is expressed in its functional form at the brush border at the time of weaning in rats.…”

“…Previous studies have suggested that DMT1 is expressed at low levels immediately after birth but that functional, fully glycosylated, and apically expressed protein is not present until later times of development (20,24). Immunohistochemical staining for DMT1 was compared in intestinal samples collected from Sprague-Dawley rats on postnatal days 1 and 21.…”

“…By postnatal day 10, DMT1 becomes localized in the apical membrane of the maturing intestine, but it is predominantly expressed in its deglycosylated/inactive form until postnatal day 20 (24). In the rat, levels of DMT1 expression continue to increase by postnatal day 40 (20), but the precise mechanisms responsible for the delivery of milk-bound iron in rats remain poorly understood. For humans, iron absorption from milk is thought to involve lactoferrin (16 -18, 21), but whether this milk protein is involved in iron absorption by rat pups is uncertain, particularly since rat enterocytes do not express lactoferrin receptors (17).…”

Manganese neurotoxicity: A focus on the neonate

“…It seems clear that duodenal absorption of metals is DMT1 regulated. However, while present early in postnatal development, it does not appear to be iron-regulated until adulthood (Leong, et al, 2003a;2003b).…”

Multiple mechanisms account for lower plasma iron in young copper deficient rats

“…Iron absorption in the suckling rat is developmentally regulated (Leong et al 2003a). Thus, dietary copper restriction during gestation and lactation may impact iron uptake across the intestine differently than a postweanling model of dietary copper limitation.…”