Received for publication June 18, 2007.
Revised September 27, 2007.
Accepted for publication September 27, 2007.

Regulation of cytochrome P450 2A6 protein expression by skatole, indole and testicular steroids in primary cultured pig hepatocytes

Abstract

Cytochrome P4502A6 (CYP2A6) is one of the enzymes involved in the hepatic metabolism of a naturally produced compound, skatole in the pig. Low CYP2A6 activity has been linked to excessive accumulation of skatole in pig adipose tissue and development of the phenomenon "boar taint". CYP2A6 activity varies between males and females, suggesting the involvement of sex hormones in regulation of the enzyme activity and/or expression. The present study investigated whether pig hepatic CYP2A6 protein expression is regulated by the testicular steroids testosterone, androstenone or estrone sulphate, using primary cultured hepatocytes as a model system. The study has also examined whether CYP2A6 expression can be modulated by the boar taint compounds, skatole and indole. The research has established that androstenone inhibits CYP2A6 protein expression at the concentration of 1, 10 and 100 nM by 55%, 37 % and 44% respectively. In contrast to androstenone, skatole and indole (final concentration 1, 10 and 100 nM) had a stimulatory effect on CYP2A6 expression. The effect of indole was more pronounced compared with the effect of skatole (maximum induction by 145% and 70% respectively). Estrone sulphate and testosterone did not have a significant effect on CYP2A6 protein level. This is, as far as we know, the first communication which reports the regulation of pig hepatic CYP2A6 expression by steroids and boar taint compounds. The hormonal modulation of CYP2A6 expression might contribute to gender-related differences in pig hepatic CYP2A6 activity and skatole accumulation in pig adipose tissue.

Key words: CYP2A, cytochrome P450, isolated hepatocytes