Constitutive and induced expression by pyridine and beta-naphthoflavone ofrat CYP1A is sexually dimorphic

Adult male and female Sprague-Dawley rats were compared in terms of the con stitutive levels and inducibility of CYP1A1 and CYP1A2 (CYP1A) in lung, kid ney, and liver. CYP1A were induced by i.p. treatment with pyridine (75 mg/k g per day) or beta-naphthoflavone (beta NF; 25 mg/kg per day) for two conse cutive days and analyzed catalytically (via O-dealkylation of resorufin eth ers), at the protein level (by Western blot analysis) and at the mRNA level (by Northern blot analysis). In untreated rats, CYP1A1 protein and its mRN A were detectable only in the lung and kidney of females but not males, whe reas CYP1A2 protein and its mRNA were detectable only in the liver in eithe r gender. Pyridine treatment upregulated CYP1A1 mRNA and its protein in the lung, kidney and liver in female rats, and upregulated the mRNA but not th e protein in the lung and liver in male rats. Conversely, pyridine induced both CYP1A2 mRNA and protein in the liver in female rats, whereas it induce d the protein but not its mRNA in the liver in male rats. No gender differe nce was observed in the plasma elimination rate of administered pyridine. b eta NF, in contrast to pyridine, induced CYP1A proteins, activities, and mR NA to higher levels in male than in female rats. The results show that the constitutive as well as inducible expression of CYP1A is sexually dimorphic in the Sprague-Dawley rat, with females being more responsive than males t o induction by pyridine but with males being more responsive than females t o induction by beta NF. The findings support the involvement of different m echanisms in CYP1A induction by pyridine and beta NF.