Hepatic CYP1A Induction in 3-Methylcholanthrene-Treated Transgenic Rats with Insufficient Blood Growth Hormone

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We have shown that the Mini rat, a transgenic rat strain carrying the antisense transgene for rat growth hormone, is a useful model to investigate the role of growth hormone in the expression of hepatic microsomal cytochrome P450s (CYPs). However, the induction of CYP isoforms by hepatic enzyme inducers in Mini rats has not been investigated. We selected two enzyme inducers, 3-methylcholantherene (2 mg/kg/day, i.p.) and phenobarbital (5 mg/kg/day, p.o.), and administered them to male Mini rats and their parental strain, Wistar rats, for 3 days. Enzyme activity assays and immunohistochemistry showed no differences in the expressions of CYP1A and CYP2B between untreated Wistar and Mini rats. 3-Methylcholanthrene administration induced CYP1A in both strains, but the induction was significantly higher in the Mini rat liver than in the Wistar rat liver. Phenobarbital administration increased CYP2B activity in both strains by more than 20-fold over their respective controls. Although there was no difference in the CYP2B immunohistochemistry between the two strains given phenobarbital, the CYP2B activity of phenobarbital-treated Mini rats was significantly higher than that of phenobarbital-treated Wistar rats. These results suggest that growth hormone may play a role in the hepatic enzyme induction.
日本毒性病理学会の論文
2001-06-30