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

D. P. Huang; G. J. Cote; R. J. Massari; J. F. Chiu

doi:10.1093/nar/13.11.3873

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

D. P. Huang, G. J. Cote, R. J. Massari, J. F. Chiu

Endocrine Neoplasia & HD

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23 Scopus citations

Abstract

The effect of dexamethasone on rat α-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.

Original language	English (US)
Pages (from-to)	3873-3890
Number of pages	18
Journal	Nucleic acids research
Volume	13
Issue number	11
DOIs	https://doi.org/10.1093/nar/13.11.3873
State	Published - Jun 11 1985

ASJC Scopus subject areas

Genetics

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title = "Dexamethasone inhibits α-fetoprotein gene transcription in neonatal rat liver and isolated nuclei",

abstract = "The effect of dexamethasone on rat α-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.",

author = "Huang, {D. P.} and Cote, {G. J.} and Massari, {R. J.} and Chiu, {J. F.}",

note = "Funding Information: ACKNOWLEDGEMENTS We thank Dr. Thomas Sargent for providing pRAF87 and pRSA57 clones and Dr. Gunther Schutz for the pTAT clone. We also thank Mr. Robert Shaw for his technical assistance in the preparation of this manuscript. We are grateful to Dr. Jeffry Cook for his critical review of this paper. G.J. Cote 1s a trainee of Cancer Biology Training Grant T32-09286. This work was supported by NIH grant #PHS R01 CA 25098.",

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doi = "10.1093/nar/13.11.3873",

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AU - Huang, D. P.

AU - Cote, G. J.

AU - Massari, R. J.

AU - Chiu, J. F.

N1 - Funding Information: ACKNOWLEDGEMENTS We thank Dr. Thomas Sargent for providing pRAF87 and pRSA57 clones and Dr. Gunther Schutz for the pTAT clone. We also thank Mr. Robert Shaw for his technical assistance in the preparation of this manuscript. We are grateful to Dr. Jeffry Cook for his critical review of this paper. G.J. Cote 1s a trainee of Cancer Biology Training Grant T32-09286. This work was supported by NIH grant #PHS R01 CA 25098.

PY - 1985/6/11

Y1 - 1985/6/11

N2 - The effect of dexamethasone on rat α-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.

AB - The effect of dexamethasone on rat α-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.

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

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