estrone-sulfate and indole

The objective of this study was to evaluate the long-term effect of a gonadotropin-releasing hormone (GnRH) vaccine, Improvac (Pfizer Ltd.), on the levels of GnRH antibodies, testosterone, estrone sulphate (E1S) and androstenone, as well as skatole and indole in male pigs. Additionally, the long-term effect of immunocastration on social and sexual behaviour was studied. Male pigs were assigned to two treatment groups: a treatment group given two doses of Improvac (n=12) and a control group of entire male pigs (n=12). The pigs were kept either 16 or 22 weeks after vaccination. Blood samples were collected five or six times; prior to both first and second vaccination, then three or four times during the 16 or 22 week period after second vaccination. Immunocastration significantly reduced levels of testosterone and E1S in plasma, and levels of androstenone in fat (P<0.001 for all). Skatole and indole levels in plasma and fat were also lower in immunocastrated pigs than in entire male pigs. These effects lasted up to 22 weeks after the second vaccination. Testis weight and bulbourethral gland length were lower in immunocastrated pigs at slaughter and these pigs showed less social, manipulating and aggressive behaviour than entire male pigs. The immunocastrated pigs remained sexually inactive throughout the study. Our study represents a further step in the evaluation of the effectiveness of Improvac as an alternative to surgical castration of entire male pigs. It shows that Improvac may have an extended effect compared with that currently implied by the directions for use.

Topics: Adipose Tissue; Androsterone; Animals; Antibodies; Bulbourethral Glands; Estrone; Gonadotropin-Releasing Hormone; Indoles; Male; Orchiectomy; Organ Size; Sexual Behavior, Animal; Skatole; Swine; Testis; Testosterone; Vaccines

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