Cytochrome P450 sex differences in minipigs and conventional pigs

Minipigs have become a popular alternative to the traditional non-rodent sp ecies although little information is available on their P450 system. The to tal P450. the enzyme activity and immunochemical levels or. some of the mos t important drug metabolizing isoenzymes CYP1A2, CYP2A6, CYP2C19, CYP2D6, C YP2E1 and CYP3A4 were measured in liver microsomes from 8 minipigs and 12 c onventional pigs of both sexes and castrate conventional pigs. The mRNA exp ression was analyzed for 3 isoenzymes: CYP1A2, CYP2A6 and CYP2E1. The total P450 activity was slightly higher in minipigs compared to conventional pig s but no sex differences were detected. CYP1A2 activity was 4 times higher in female than in male minipigs. The activity of the male minipigs possesse d the same activity as were identical to the conventional females. males an d castrates. The activity of CYP2E1 was 4 times higher in female than in ma le minipigs and 2 times higher in female than in male pies. No activity of CYP2D6 or CYP2C19 could be detected. The CYP3A4 activity detected in minipi gs was higher than the activity in conventional pigs. A slight sex differen ce was seen in both strains. Correlations between enzyme activity and immun ochemical levels were found for CYP1A2, CYP2A6 and CYP3A4 but not for CYP2E 1. The mRNA concentration of CYP1A2, CYP2A6 and CYP2E1 was determined becau se the activity of these enzymes showed marked sex differences. A Spearman ranking correlation analysis between mRNA expression and enzyme activity sh owed a weak correlation for CYP2A6, but not for CYP1A2 and CYP2E1. These re sults seem to indicate that CYP2A6 could be transcriptionally regulated, wh ereas CYP1A2 might be post-transcriptionally regulated.