Integration and control of metabolism of boar taint compounds

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This research is designed to obtain a more complete understanding of factors affecting the accumulation of odorous compounds, skatole and androstenone, which cause off-odours and off-flavors (boar taint) in pork produced from uncastrated male pigs. Male pigs are routinely castrated at an early age to prevent boar taint, but castration raises concerns about animal welfare, as well as decreases the productivity of pig production. The results of this research could be used to develop alternative methods to control boar taint so that castration can be eliminated. We will study the role of different porcine cytochrome P450 (CYP450s) enzymes in the metabolism and clearance of skatole, which is produced by the gut microflora from tryptophan. In some male pigs, the hepatic metabolism of skatole in compromised, so that high levels of skatole accumulate in fatty tissue, resulting in boar taint. Androstenone is produced by the testis near maturity and acts as a sex pheromone. It is converted to sulphoconjugates and glucuronides by phase II conjugation reactions in the liver and excreted in the bile. We have recently shown that levels of androstenone can be reduced by including non-nutritive binding agents such as activated carbon in the diet. These compounds likely prevent the reabsorption of androstenone from the digestive tract via the enterohepatic circulation, and we now plan to carry out detailed studies to confirm this. The nuclear receptors CAR, PXR and FXR regulate the expression of CYP450s as well as phase II enzymes and we plan to characterize their central role in the regulation of genes that are involved in the metabolism of androstenone and skatole. We have also found that these receptors have several splice variants, and some of these produce dramatic and specific dominant positive or dominant negative effects on the activity of the wild type receptor; we plan to investigate the molecular mechanisms behind these effects. This work will develop a better understanding of how to control the problem of boar taint, but the pig is not only a valuable food animal but is also recognized as an excellent model for toxicological and pharmacological studies of relevance to humans.