CONTROL OF CELLULAR IRON HOMEOSTASIS BY IRON-RESPONSIVE ELEMENTS IN-VIVO

It has recently been proposed that cellular iron homeostasis in mammal ian cells is regulated at the post-transcriptional level by the recipr ocal control of transferrin receptor and ferritin mRNA expression via an iron-regulatory factor. This iron-regulatory factor has been shown to be a cytoplasmic aconitase which can bind to iron-responsive elemen ts in the corresponding mRNAs with greater or lesser affinity as a fun ction of the iron status of the cell. In the present study, we show th at in vivo the affinity of iron-regulatory factor for iron-responsive elements in liver reflects the long-term iron status of the tissue in animal models for iron overloading and iron deficiency, when combined with altered transferrin saturation and serum iron levels. In contrast hepatic iron overload achieved without altering such haematopoeitic i ndices, had a less pronounced effect. In both spleen and heart, the af finities of iron-regulatory factor changed in parallel with both alter ed iron status and haematological markers. In brain and duodenum, ther e were no consistent changes in iron-regulatory-factor activity with i ron loading or depletion. Iron-regulatory-factor activity in kidney re sponded in an as yet unexplained manner.