Transferrin gene expression. Regulation of mRNA transcription in chick liver by steroid hormones and iron deficiency.

Abstract

scription in vitro in the presence of (CU-~~P)UTP. The 32P transcripts then were hybridized to immobilized recom- binant DNA containing the double-stranded transferrin cDNA sequence. Transcripts from control liver nuclei contained 0.009% transferrin mRNA; iron deficiency and estrogen treatment caused an increase in the rate of transferrin mRNA synthesis of 1.5- and 2-fold, re- spectively. These increases in the transcriptional activ- ity of the transferrin gene were accompanied by in- creases in the cellular level of transferrin mRNA, the rate of transferrin synthesis, and the concentration of serum transferrin. The combined treatment of iron de- ficiency and estrogen resulted in a synergistic response in all parameters of transferrin induction, including the rate of transferrin mRNA synthesis which increased 3.2-fold to 0.029% of total RNA synthesis. Although estrogen stimulation leads to a 40% decrease in liver non-heme iron, the estrogen-mediated induction of transferrin mRNA was not blocked when liver iron was maintained at high levels with injected ferritin. These results suggest that iron deficiency and estrogen inter- act with the liver transferrin gene through separate regulatory mechanisms. The transferrin gene is also expressed in oviduct and we compare and discuss the tissue-specific response of this gene to iron and steroid hormones.