Hormonal regulation of serine dehydratase gene expression in liver and kidney of the adrenalectomized rat.
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 run-on 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kanamoto
R
R
McArdle Laboratory for Cancer Research, Department of Oncology, Medical School, University of Wisconsin, Madison 53706.
Su
Y
Y
Pitot
H C
HC
D000315:Adrenalectomy; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D012695:L-Serine Dehydratase / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003907:Dexamethasone; D005934:Glucagon; D012695:L-Serine Dehydratase