Nuclear receptors and the integrative 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 (3-methylindole) and the 16-androstene steroids (especially androstenone), in pigs. These compounds cause undesirable off-odors and off-flavors (boar taint) in pork meat produced from uncastrated male pigs. The 16-androstene steroids are produced by the testis near maturity and act as sex pheromones, while skatole is produced by bacteria in the gut and contributes to the characteristic odour of pig manure. 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 growth efficiency and lean yield of the pigs.The goal of this research is to understand the regulation of the biochemical and physiological processes that affect the accumulation of boar taint compounds in pigs. We plan to further investigate aspects of the metabolism of androstenone and skatole including: examining the role of cytochrome b5 isoforms and CYP17 in the synthesis of 16-androstene steroids; determining the role of various cytochrome P450 isoforms in skatole metabolism; determining the potential role of sulfatase in androstenone accumulation in fat and investigating the role of glucuronidation and the enterohepatic circulation in androstenone accumulation. We also plan to study the integration and regulation of the metabolism of androstenone and skatole via nuclear receptors (CAR and PXR) including: identifying the endogenous compounds that affect CAR and PXR in the boar; conducting in vivo studies with CAR and PXR agonists to determine the role of these receptors in boar taint and further characterizing the genes that are regulated by CAR and PXR. This information could be used to find alternative methods to control the boar taint problem so that castration can be eliminated.