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.

Highlights

  • Transferrin Gene ExpressionREGULATION OF mRNA TRANSCRIPTION IN CHICK LIVER BY STEROID HORMONES AND IRON DEFICIENCY *

  • For exam- Acknowledgments-We would like to thank Ms Betty Josephson ple, after 4 days of estrogen treatment, liver wet weight has for performing serum and liver iron determinations and Dr Clement increased 2-fold, the rate of albumin synthesis has decreased [3], and the egg yolk protein, vitellogenin, has become the

  • In agreement with the resultsof Morgan[19], we find that estrogen causes a dramatic

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Summary

Transferrin Gene Expression

REGULATION OF mRNA TRANSCRIPTION IN CHICK LIVER BY STEROID HORMONES AND IRON DEFICIENCY *. Estrogen and iron deficiency regulate the synthesis Inaddition, a recombinant plasmid has been constructed of transferrin in chick liver by causing a specific in- which contains the transferrin cDNA sequence [4] and this crease in transcription of the transferrin gene. 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, respectively. Transferrin mRNA was not blocked whenliver iron was Glucocorticoids elicit an induction in bothtissues but, as maintained at high levels with injected ferritin These with estrogen, the response in liver is approximately 2-fold results suggest that iron deficiency and estrogen inter- and occurs over 4 days, whereas the oviduct responds rapidly act with the liver transferrin gene through separate and transferrin mRNA levels increase more than 10-fold.’. Signal peptides [2] and cDNA cross-hybridization studies [3]

EXPERIMENTA LP ROCEDURES
Brain Pancreas Kidney Spleen Heart Lung Intestine
RESULTS
The combined effects of estrogen and iron deficiency on transferrinregulation
No hormone
Dexamethasone plus ferritin Ferritin alone
DISCUSSION
Regulation of TransferrinmRNA Synthesis
Tf eramnnsmRNA sis
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