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

Estrogen and iron deficiency regulate the synthesis of transferrin in chick liver by causing a specific increase in transcription of the transferrin gene. The relative rate of synthesis of transferrin mRNA was measured by allowing isolated nuclei to continue transcription in vitro in the presence of [CU-~~P]UTP. The 32P transcripts then were hybridized to immobilized recombinant 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 1.5and 2-fold, respectively. These increases in the transcriptional activity of the transferrin gene were accompanied by increases in the cellular level of transferrin mRNA, the rate of transferrin synthesis, and the concentration of serum transferrin. The combined treatment of iron deficiency 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 interact 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.