Suppression in the expression of a male-specific cytochrome P450, P450-male: difference in the effect of chemical inducers on P450-male mRNA and protein in rat livers.
Hypophysectomy of male adult rats caused a 70% decrease in the hepatic level of mRNA hybridized to two specific oligonucleotide probes for the sequence of coding and 3'-noncoding regions of P450(M-1) (H. Yoshioka et al., (1987) J. Biol. Chem. 262, 1706-1711), which corresponds to P450-male. Treatment of hypophysectomized male and female rats with subcutaneous injection of human growth hormone twice a day for 7 days increased the mRNA to a level similar to that of normal male rats. In contrast, the mRNA was decreased by treatment with continuous infusion. These results correlated well with those on the amounts of P450-male protein, indicating that growth hormone regulates the hepatic level of P450-male protein mainly by acting at the pretranslational step. Treatment of adult male rats with phenobarbital (PB), dexamethasone (Dex), or 3-methylcholanthrene (MC) decreased the content of P450-male protein by 68, 36, and 46%, respectively. The content of P450-male protein was also decreased to 65% in Dex-treated hypophysectomized male rats, but was not changed by treatment of hypophysectomized male rats with PB or MC, suggesting that PB and MC decrease P450-male protein through a pituitary growth hormone-mediated process. However, the level of mRNA hybridizable to the P450-male oligonucleotide probe was not decreased, but rather it increased in PB- or Dex-treated hypophysectomized male rats. A similar inconsistent change in protein and mRNA was also observed in PB-treated normal rats. These results indicate that PB and Dex have an additional effect of increasing the hepatic level of the specific mRNA of P450-male/(M-1) or a closely related form. Noncoordinate changes in the level of P450-male protein and mRNA also suggest that the hepatic level of P450-male protein is regulated by plural mechanisms: pretranslational and translational regulation in which pituitary growth hormone and/or other endocrine factors are involved.
Shimada
M
M
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Murayama
N
N
Yamauchi
K
K
Yamazoe
Y
Y
Kato
R
R
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D007016:Hypophysectomy; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital