Regulation of cytochrome P-450b and P-450e mRNA expression in the developing rat. Hybridization to synthetic oligodeoxyribonucleotide probes.
We conducted solution hybridization and Northern blot experiments utilizing synthetic 18'-mer oligodeoxyribonucleotides complementary to two major rat hepatic phenobarbital-inducible cytochrome P-450s, P-450b and P-450e, to assess their mRNA expression during rat development. At all ages studied, with one exception (i.e. in day 22 neonates), P-450b mRNA was not detected in control animals. However, traces of P-450e message were observed in control animals on day 22 and persisted to adulthood. Phenobarbital pretreatment caused marked increases in hepatic mRNA for both P-450s as early as 22 days after conception. No increases were observed in RNA isolated from phenobarbital-pretreated day 10 or 19 rats. In general, the inducible levels of P-450b and P-450e mRNA increased as a function of age. The age-dependent increase in responsiveness to phenobarbital was associated with an age-dependent decrease in the ratio of P-450b to P-450e mRNA levels. The levels of P-450b/P-450e varied from a ratio of 19 at day 22 of development to a ratio of 5 at day 62 of development. Maximal levels of phenobarbital-induced hepatic RNA for both isozymes occurred 24 days after birth (day 46 of development), at which time P-450b and P-450e mRNAs accumulated to levels 2.4- and 1.8-fold greater, respectively, than levels found in comparably induced adult rat liver. Northern blot analyses indicated that the major mRNA species hybridizing to either the P-450b or P-450e oligomers in all age groups studied was approximately 1.8 kilobases.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital