Posttranscriptional regulation of coumarin 7-hydroxylase induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole

Biochemistry. 1991 Aug 13;30(32):8041-5. doi: 10.1021/bi00246a023.


The induction mechanism by pyrazole or phenobarbital of coumarin 7-hydroxylase (cytochrome P450coh) was investigated in DBA/2J male mice. The P450coh mRNA in the pyrazole-induced mice was increased gradually to a 20-fold higher level within 48 h, yet transcription of the P450coh gene was not affected. The half-life of P450coh mRNA, on the other hand, was at least 4-fold longer in the pyrazole-induced DBA/2J (approximately 6.0 h) than in control DBA/2J (approximately 1.5 h) male mice. The stabilization of P450coh mRNA, therefore, is the primary mechanism for the induction by pyrazole of coumarin 7-hydroxylase. Phenobarbital, on the other hand, regulates the induction either translationally or posttranslationally. This drug affected neither the P450coh mRNA nor the P450coh gene's transcription levels in the DBA/2J male mice, although Western blots showed approximately a 3-fold increase of the P450coh protein in the liver microsomes of the drug-treated mice. The results indicate, therefore, that both phenobarbital and pyrazole regulate the P450coh induction posttranscriptionally; the former inducer enhances the translational efficiency of P450coh mRNA or alters the degradation rate of P450coh aproprotein, while the latter stabilizes P450coh mRNA.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases*
  • Blotting, Northern
  • Cell Nucleus / drug effects
  • Cell Nucleus / physiology
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics*
  • Enzyme Induction
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Kinetics
  • Liver / drug effects
  • Liver / enzymology*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mixed Function Oxygenases / biosynthesis
  • Mixed Function Oxygenases / genetics*
  • Phenobarbital / pharmacology*
  • Pyrazoles / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics*
  • Transcription, Genetic* / drug effects
  • Xenobiotics / pharmacology*


  • Pyrazoles
  • RNA, Messenger
  • Xenobiotics
  • pyrazole
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2A6
  • Phenobarbital