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.