title: Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker rats: effect of phenobarbital treatment.
abstract: The present study determined the effect of genetic obesity and phenobarbital (PB) treatment on the expression and regulation of the hepatic cytochrome P450 enzyme (CYP2C11) in Fa/? and fa/fa Zucker rats. Hepatic CYP2C11 levels as determined by Western immunoblotting and associated enzymatic activity (testosterone oxidation at the 2 alpha position) were significantly lower in untreated fa/fa Zucker rats compared with that observed in Fa/? Zucker rats. There was no significant difference in the constitutive CYP2C11 steady-state mRNA level hybridizable to the cDNA (P450 16 alpha) or specific oligonucleotide probe (Northern and slot blot analyses) between fa/fa and Fa/? Zucker rats. The depressed constitutive CYP2C11 protein levels in fa/fa rats may be attributed to their low plasma testosterone and growth hormone levels; however, lack of differences in CYP2C11 steady-state mRNA suggest post-transcriptional regulatory mechanism(s). Treatment with PB further suppressed hepatic CYP2C11 protein levels and activities in both fa/fa and Fa/? Zucker rats in comparison with that seen in controls. The level of CYP2C11 steady-state mRNA was significantly higher after treatment with PB in Fa/? Zucker rats, while no change was observed in fa/fa animals. The mechanism by which PB treatment fails to increase CYP2C11 steady-state mRNA levels in the fa/fa Zucker rat is unknown; however, it may share a common molecular basis with the defect in nuclear transcription rate previously observed with CYP2B1/2B2.
authors.affiliation: Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536.
authors.forename: A M
authors.initials: AM
authors.lastname: Bandyopadhyay
authors.forename: I
authors.initials: I
authors.lastname: Chaudhary
authors.forename: L W
authors.initials: LW
authors.lastname: Robertson
authors.forename: B
authors.initials: B
authors.lastname: Gemzik
authors.forename: A
authors.initials: A
authors.lastname: Parkinson
authors.forename: R A
authors.initials: RA
authors.lastname: Blouin
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D004247:DNA; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006579:Heterozygote; D006720:Homozygote; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects; D008969:Molecular Sequence Data; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D013739:Testosterone / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D013739:Testosterone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D010634:Phenobarbital