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Hormonal Regulation of Serine Dehydratase Gene Expression in Liver and Kidney of the Adrenalectomized Rat

McArdle Laboratory for Cancer Research, Departments of Oncology and Pathology, The Medical School, University of Wisconsin Madison, Wisconsin 53706

Address requests for reprints to: Dr. Henry C. Pitot, McArdle Laboratory for Cancer Research, Departments of Oncology and Pathology, The Medical School, University of Wisconsin,1400 University Avenue, Madison, Wisconsin 53706.

Abstract

We have previously demonstrated that glucagon but not dexamethasone could induce serine dehydratase (SDH: EC.4.2.1.13) in liver, and either glucagon or dexamethasone could induce the enzyme in kidney of normal rats. The mechanism(s) of the hormonal regulation of SDH gene expression in liver and kidney was further studied using adrenalectomized rats. Simultaneous administration of glucagon and dexamethasone induced the activity, rate of SDH synthesis, and accumulation of SDH mRNA in both liver and kidney of the rat. The increased SDH activity was reflected by changes in the amount of enzyme protein and in the rate of SDH protein synthesis, both parameters closely paralleling the changes in the levels of SDH mRNA. The rates of transcription of the SDH gene as measured in runon experiments with isolated nuclei were also increased by the administration of these hormones. These results indicate that the expression of the SDH gene was regulated primarily at the transcriptional level under these conditions. When glucagon or dexamethasone was injected separately into adrenalectomized rats, significant increases in the levels of SDH mRNA and the rate of SDH gene transcription were observed in liver. Although glucagon was more effective than dexamethasone, both hormones were required for the maximal induction of SDH gene transcription in liver. In contrast, dexamethasone alone effectively increased the rate of SDH gene transcription in kidney. Glucagon had no effect on SDH induction in kidney, nor did it enhance the effect of dexamethasone. Primer extension analysis by using RNAs prepared from liver and kidney indicated an identical start site of transcription of the SDH gene in these tissues. These studies demonstrated that the hormonal regulation of SDH in the rat exhibits tissue-specific requirements when the expression of the gene is compared in liver and kidney.

FOOTNOTES

The studies reported herein were supported in part by Grants CA-07175, CA-22484, and CA-45700 from the National Cancer Institute.

^* Present Address: Department of Nutrition, The Jikei University School of Medicine, Tokyo, Japan.

Received for publication June 18, 1991. Revision received August 28, 1991. Accepted for publication August 29, 1991.