GENDER DIFFERENCES IN ETHANOL OXIDATION AND CYTOCHROME P4502E1 CONTENT AND FUNCTIONS IN HEPATIC MICROSOMES FROM ALCOHOL-PREFERRING AND NONPREFERRING RATS

1. We have studied the hepatic microsomal metabolism of ethanol (MEOS) , CYP2E1 expression and catalytic activity, and the response to phenob arbital (PB) induction or CCl4 challenge in rats of either sex genetic ally selected for their preference (P) or aversion (NP) for ethanol. 2 . In P versus NP females, the amount of both total cytochrome P450 and P450 binding to metyrapone was lower, whereas the activities of MEOS, aniline 4-hydroxylase (4-AOH), and 4-nitrophenol hydroxylase (PNP-OH) as well as the level of immunodetectable CYP2E1 content were consiste ntly higher. By contrast, no substantial differences were observed bet ween P and NP males. 3. Despite an apparent down-regulation of CYP2E1 expression occurring in all rats as a result of PB induction, P female s maintained higher 2E1 levels and showed enhanced MEOS, 4-AOH and PNP -OH activities with respect to NP females. No such changes were detect ed in the male counterparts. 4. No sex-related differences in CCl4-med iated inhibition of monooxygenase or MEOS activities were evident betw een P and NP animals. 5. These results indicate that, in females only, the behavioural trait of ethanol preference is apparently associated not only with higher constitutive levels of CYP2E1 and rate of microso mal metabolism of ethanol but also with altered susceptibility to PB i nduction.