Bone Christine, Squires E James
Department of Animal Biosciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Animals (Basel). 2025 Jul 25;15(15):2199. doi: 10.3390/ani15152199.
The nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), and farnesoid X receptor (FXR) regulate the hepatic metabolism of androstenone, a testicular steroid that accumulates in the fat of intact male pigs and causes boar taint. This study evaluated natural product-derived compounds and conventional agonists targeting these nuclear receptors for their effects on androstenone metabolism in primary hepatocytes from slaughter-weight boars, to assess their potential as treatments for boar taint. Cells were incubated with natural products, conventional agonists, or dimethyl sulfoxide (DMSO; control), then being treated with androstenone. Culture media and cells were analyzed to assess changes in androstenone metabolism and gene expression. was upregulated by treatments targeting both PXR and CAR and downregulated by FXR agonists. Additionally, and were downregulated by compounds targeting PXR/CAR, while and were upregulated and downregulated by treatments acting on FXR. The natural products diallyl sulfide (DAS) and (Z)-guggulsterone (GUG) increased overall androstenone metabolism (DAS, GUG) and the production of Phase I androstenol metabolites (DAS), but only in hepatocyte culture replicates that responded positively to these treatments. Although gene expression was similar between positive-response and negative/non-responsive replicates following treatments, negative/non-responsive replicates for several treatments had higher basal expression of , , and and lower basal expression of , , and compared to positive-response replicates. These findings suggest that DAS and GUG may be promising treatments for boar taint, specifically in animals with lower basal rates of androstenone metabolism and higher expression of key nuclear receptors.
核受体孕烷X受体（PXR）、组成型雄甾烷受体（CAR）和法尼酯X受体（FXR）调节雄烯酮的肝脏代谢，雄烯酮是一种睾丸类固醇，会在未阉割公猪的脂肪中蓄积并导致公猪异味。本研究评估了靶向这些核受体的天然产物衍生化合物和传统激动剂对屠宰体重公猪原代肝细胞中雄烯酮代谢的影响，以评估它们作为公猪异味治疗方法的潜力。将细胞与天然产物、传统激动剂或二甲基亚砜（DMSO；对照）一起孵育，然后用雄烯酮处理。分析培养基和细胞以评估雄烯酮代谢和基因表达的变化。靶向PXR和CAR的处理使其上调，而FXR激动剂使其下调。此外，靶向PXR/CAR的化合物使 和 下调，而作用于FXR的处理使 和 上调， 下调。天然产物二烯丙基硫醚（DAS）和（Z）-古甾酮（GUG）增加了雄烯酮的总体代谢（DAS、GUG）以及I相雄烯醇代谢物的产生（DAS），但仅在对这些处理有阳性反应的肝细胞培养复制品中。尽管处理后阳性反应和阴性/无反应复制品之间的基因表达相似，但与阳性反应复制品相比，几种处理的阴性/无反应复制品中 、 和 的基础表达较高，而 、 和 的基础表达较低。这些发现表明，DAS和GUG可能是治疗公猪异味的有前景的方法，特别是在雄烯酮代谢基础速率较低且关键核受体表达较高的动物中。
