Regulation of CYP2A6 protein expression by skatole, indole, and testicular steroids in primary cultured pig hepatocytes.
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 male and female animals, 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 sulfate 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 concentrations, 1, 10, and 100 nM) had a stimulatory effect on CYP2A6 expression. The effect of indole was more pronounced than that of skatole (maximum induction by 145 and 70%, respectively). Estrone sulfate and testosterone did not have a significant effect on CYP2A6 protein level. This is, as far as we know, the first communication to report 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.
Chen
Gang
G
Department of Food Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Cue
Rebecca-Ayme
RA
Lundstrom
Kerstin
K
Wood
Jeffrey D
JD
Doran
Olena
O
D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D015153:Blotting, Western; D002478:Cells, Cultured; D065637:Cytochrome P-450 CYP2A6; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D012862:Skatole / Q000494:pharmacology*; D013552:Swine; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D045165:Testosterone Congeners / Q000494:pharmacology*; D015854:Up-Regulation
D000736:Androstenes; D007211:Indoles; D045165:Testosterone Congeners; C000214:androst-16-en-3-one; D004970:Estrone; D013739:Testosterone; C030374:indole; D012862:Skatole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; C017296:estrone sulfate