230 The relationship between hormone status and the metabolism of androstenone and skatole in isolated porcine hepatocytes

Abstract Surgical castration is a significant welfare concern within the swine industry; however, it is currently the most effective method to prevent boar taint, which is a meat quality issue that develops in entire male pigs due to the accumulation of androstenone and skatole in the fat. Metabolism of the boar taint compounds occurs within the liver and promotes their excretion, ultimately reducing the extent of their accumulation in the fat. Previous research has demonstrated that plasma concentrations of estrone sulfate (E1S), which are indicative of steroid hormone status in the boar, are highly variable between individual animals of similar live body weights at slaughter. Testicular steroids are known to influence the activity and expression of some enzymes regulating the metabolism of skatole, but the effect of hormone concentrations on the entire expression profile of enzymes responsible for boar taint metabolism has not been characterized. Therefore, the objective of this study was to relate plasma E1S concentrations at slaughter to expression levels of genes regulating the metabolism of androstenone and skatole and their respective metabolite profiles in isolated hepatocytes, to further characterize the relationship between hormone status and boar taint metabolism. Blood and liver samples were collected from 5-mo-old crossbred [(Yorkshire x Landrace) x Duroc] boars (n = 8)] at slaughter. Plasma E1S concentrations were quantified using a radioimmunoassay and gene expression in the liver was evaluated by RT-qPCR. Hepatocytes were also isolated and incubated with androstenone or skatole, with metabolite concentrations in the incubation media quantified by high-performance liquid chromatography. Statistical analysis was performed using Pearson correlation. Plasma E1S concentrations at slaughter ranged from 2.2-108.5 ng/mL and were positively correlated with overall skatole metabolism (r = 0.77, P = 0.0265), the production of the Phase I skatole metabolites 3-methyloxindole (3MOI; r = 0.80, P = 0.0183), and 3-hydroxy-3-methyloxindole (HMOI; r = 0.73, P = 0.0413), as well as expression levels of CYP2C33 (r = 0.88, P = 0.0042), CYP2C49 (r = 0.78, P = 0.0221), and CYB5R1 (r = 0.80, P = 0.0165), which regulate skatole metabolism. A strong positive relationship was also identified between overall skatole metabolism and the production of 3MOI (r = 0.96, P = 0.0001) and HMOI (r = 0.93, P = 0.001). Androstenone metabolism primarily resulted in the production of Phase II glucuronide metabolites, but the levels produced were not related to E1S concentrations or gene expression levels. Taken together, these results demonstrate that plasma E1S concentrations are related to the rate of skatole, but not androstenone, metabolism in mature boars. Additional research is required to assess the potential of E1S concentrations as a biomarker for the rate of skatole metabolism in vivo and establish thresholds that could be used to identify boars with high and low rates of metabolism. This may provide an opportunity to develop targeted treatments for boar taint based on the metabolic status of the animal.