A novel gender-related difference in the constitutive expression of hepatic cytochrome P4501A subfamily enzymes in Meishan pigs

Constitutive expression levels of hepatic CYP1A subfamily enzymes, CYP1A1 and CYP1A2, in male and female Meishan pigs were examined at levels of the mRNA, protein, and enzyme activity. In mature (5-month-old) pigs, levels of hepatic CYP1A1 and CYP1A2 mRNAs, as determined by RT-PCR, were much higher in females than in males, but those of castrated male pigs were equivalent to female pigs. The gender-related differences in the levels of CYP1A mRNAs closely correlated with those of the corresponding apoproteins determined by Western blotting. Hepatic enzyme activities not only for the O-dealkylation of ethoxyresorufin and methoxyresorufin (typical substrates for CYP1A1 and CYP1A2, respectively) but also for the mutagenic activation of benzo[a]pyrene and 2-amino-6-methyl-dipyrido[1,2-a; 3′,2′-d]imidazole (typical substrates for CYP1A1 and CYP1A2, respectively) were also much greater in female and castrated male pigs than in male pigs. In immature (1-month-old) pigs, no such gender-related differences were observed, and their gene expression levels of the CYP1A subfamily enzymes were almost the same as those of mature female pigs. Furthermore, treatment of immature pigs with testosterone resulted in a drastic decrease in the levels of the CYP1A1 and CYP1A2 mRNAs in both sexes. The present findings demonstrate a gender-related difference in the constitutive expression of hepatic CYP1A subfamily enzymes in Meishan pigs and further indicate that androgen down-regulates the constitutive gene expression of the enzymes.