androst-16-en-3-one and estrone-sulfate

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.

Topics: Androstenes; Animals; Aryl Hydrocarbon Hydroxylases; Blotting, Western; Cells, Cultured; Cytochrome P-450 CYP2A6; Dose-Response Relationship, Drug; Down-Regulation; Electrophoresis, Polyacrylamide Gel; Estrone; Hepatocytes; Indoles; Male; Mixed Function Oxygenases; Skatole; Swine; Testis; Testosterone; Testosterone Congeners; Up-Regulation

This study describes the age-related variation in boar taint compounds, skatole and androstenone, and testosterone, oestradiol-17 beta (E17 beta), oestrone sulphate (ES), dehydroepiandrosterone sulphate (DHEAS), triiodothyronine (T(3)) and insulin-like growth factor-1 (IGF-1) in six boars. Three pairs of littermates of crossbred entire male pigs (from three Yorkshire x Duroc dams and one Hampshire sire) were included. Blood samples were taken at the age of 9-15 weeks and thereafter at weekly intervals from the age of 20-32 weeks. Plasma concentrations of skatole, androstenone, testosterone, E17 beta, ES, DHEAS, T(3) and IGF-1 were measured. We found that skatole levels in boars increased at the age around puberty after an increase in the levels of testicular steroids. Levels of skatole were not associated with the levels of sex steroids, T(3) and IGF-1. However, the increased level of testicular steroids is probably the underlying factor needed for high skatole levels to occur although the specific mechanism leading to increased skatole levels remains unknown.

Topics: Aging; Androstenes; Animals; Animals, Newborn; Dehydroepiandrosterone Sulfate; Estradiol; Estrone; Insulin-Like Growth Factor I; Male; Skatole; Swine; Testosterone; Triiodothyronine