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PMID: 2409527 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Dexamethasone inhibits alpha-fetoprotein gene transcription in neonatal rat liver and isolated nuclei.

Nucleic acids research ·Vol. 13 ·No. 11 ·1985-06-11 ·Pages 3873-90

Huang DP, Cote GJ, Massari RJ, Chiu JF

Abstract

The effect of dexamethasone on rat alpha-fetoprotein (AFP) expression has been further examined. Quantitation of serum AFP levels from newborns treated with dexamethasone showed a dose-response relationship between the quantity of dexamethasone administered and the reduction in AFP serum level. RNA blots, utilizing cloned AFP cDNA as probe, showed a marked reduction in AFP mRNA in dexamethasone treated livers. The extent of AFP mRNA depletion was correlated with dexamethasone dosage. The effect of dexamethasone on AFP mRNA concentration was relatively rapid; a substantial reduction occurred 12 hours after a single injection. The effect of dexamethasone appeared to be irreversible as hormone withdrawal did not cause AFP mRNA levels to rise. One putative AFP nuclear RNA precursor was identified which rapidly disappeared following dexamethasone treatment. AFP mRNA synthesis was also diminished in nuclei transcribed in vitro. The direct inhibitory effect of glucocorticoid hormone on AFP gene transcription was demonstrated in a reconstituted cell-free nuclear system.

MeSH Terms
Animals Animals, Newborn Cell Nucleus/metabolism Cloning, Molecular Cytosol/metabolism DNA/metabolism Dexamethasone/pharmacology Genes/drug effects Kinetics Liver/metabolism Liver Neoplasms, Experimental/metabolism Nucleic Acid Hybridization RNA/isolation & purification RNA, Messenger/genetics Rats Rats, Inbred Strains Receptors, Glucocorticoid/metabolism Transcription, Genetic/drug effects alpha-Fetoproteins/analysis,genetics
Chemicals
RNA, Messenger Receptors, Glucocorticoid alpha-Fetoproteins RNA Dexamethasone DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Huang D P
Cote G J
Massari R J
Chiu J F
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49 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/13.11.3873
Published
1985-06-11
Pages
3873-90
Language
English
Region
England
NLM ID
0411011
PMCID
PMC341283
Subset
IM
Grants
NCI NIH HHS · R01 CA 25098 · United States
PHS HHS · T32-09286 · United States
External Links
PubMed source DOI: 10.1093/nar/13.11.3873 PMC Full Text View journal details
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