Increase in surface expression of transferrin receptors on cultured hepatocytes of adult rats in response to iron deficiency

The effect of changes in cellular iron metabolism on the surface expression of transferrin receptors (TfR) was examined in primary cultures of hepatocytes from adult rats. Untreated control hepatocytes exhibited a single class of high affinity receptors for transferrin (KD = 40 nM), with approximately 17,000-18,000 receptors per cell. Following 24 h of treatment with the iron chelator, desferrioxamine, or with succinylacetone, an inhibitor of heme synthesis, the number of TfR at the cell surface was increased severalfold, with no significant change in receptor affinity (KD) for transferrin. When combined, the enhancing effects of the two agents were additive. Inhibition of protein synthesis by cycloheximide abolished the increase in TfR expression mediated by either agent. Hemin decreased surface TfR expression and counteracted the enhancing effects of desferrioxamine or succinylacetone on TfR expression. These results indicate that, under the culture conditions employed, 1) iron deficiency induces an increase in surface TfR and 2) modulation of the receptor population is mainly dependent on de novo synthesis of TfR.