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Nucleic Acids Research, 1981, Vol. 9, No. 24 6917-6933
© 1981


MOLECULAR BIOLOGY

Hormonal modulation of {alpha}-fetoprotein gene expression in newborn rat livers

Jen-Fu Chiu, Ronald J. Massari, Charles E. Schwartz, Natalie T. Meisler and John W. Thanassi

Department of Biochemistry, University of Vermont, College of Medicine Burlington, VT 05405, USA

Received October 26, 1981. Suppression of serum {alpha}-fetoprotein (AFP) levels in glucocorticoid treated newborn rats was investigated. Daily intraperitoneal injection of 2 µg/g body weight of dexamethasone into newborn rats greatly reduced the concentration of AFP in the serum and liver cytosol. In contrast, this treatment stimulated liver ornithine decarboxylase activity. The reduction in AFP levels is not due to a change of distribution of AFP molecular variants, inhibition of secretion of synthesized AFP by the liver or disruption of liver polysomes. Glucocorticoids decrease the AFP levels in hormonetreated rats by supressing the synthesis of AFP. The size of AFP polysomes isolated from the livers of dexamethasone-treated rats were as large as those from normal rats. However, the amount of AFP-producing polysomes in hormonetreated rat liver is only 14% of the controls. By hybridization assays, it was found that dexamethasone treated livers contained decreased amounts of AFP mRNA sequences in liver cytoplasmic and nuclear RNAs. The decreased amounts of AFP mRNA sequences in hormone-treated liver are caused by both a decrease in the rate of AFP mRNA transcription and in AFP mRNA stability.


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