Nuclear receptors and the integrative metabolism of boar taint compounds

本研究旨在更全面地了解影响猪体内恶臭化合物、粪臭素（3-甲基吲哚）和16-雄甾烯类固醇（特别是雄甾烯酮）积累的因素。这些化合物在由未阉割的雄性猪生产的猪肉中引起不期望的异味和异味（野猪味）。16-雄甾烯类固醇是由接近成熟的睾丸产生的，并作为性信息素，而粪臭素是由肠道中的细菌产生的，并导致了猪粪便的特征气味。为了防止公猪的臭味，通常在早期对公猪进行阉割，但阉割引起了对动物福利的关注，同时降低了猪的生长效率和瘦肉产量。本研究的目的是了解影响公猪臭味化合物在猪体内积累的生化和生理过程的调节。我们计划进一步研究雄甾烯酮和粪臭素的代谢方面，包括：检查细胞色素b5亚型和CYP 17在16-雄甾烯类固醇合成中的作用;确定各种细胞色素P450亚型在粪臭素代谢中的作用;确定硫酸酯酶在脂肪中雄甾烯酮积累中的潜在作用，并研究葡萄糖醛酸化和肝肠循环在雄甾烯酮中的作用积累我们还计划通过核受体（CAR和PXR）研究雄烯酮和粪臭素代谢的整合和调节，包括：鉴定影响公猪CAR和PXR的内源性化合物;用CAR和PXR激动剂进行体内研究，以确定这些受体在公猪恶臭中的作用，并进一步表征CAR和PXR调节的基因。这些信息可以用来寻找替代方法来控制公猪的污点问题，使阉割可以消除。

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.