Kliewer Steven A, Willson Timothy M
Nuclear Receptor Discovery Research, GlaxoSmithKline, 5 Moore Drive, Room V118.1B, Research Triangle Park, NC 27709, USA.
J Lipid Res. 2002 Mar;43(3):359-64.
The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection). PXR is activated by a diverse array of lipophilic chemicals, including xenobiotics and endogenous substances, and regulates the expression of cytochromes P450, conjugating enzymes, and transporters involved in the metabolism and elimination of these potentially harmful chemicals from the body. Among the chemicals that bind and activate PXR is the toxic bile acid lithocholic acid; activation of PXR, in turn, protects against the severe liver damage caused by this bile acid.Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver.
核孕烷X受体（PXR；NR1I2）是机体抵御化学损伤（化学保护）防御机制的一个重要组成部分。PXR可被多种亲脂性化学物质激活，包括外源性物质和内源性物质，并调节细胞色素P450、结合酶以及参与这些潜在有害化学物质在体内代谢和清除的转运蛋白的表达。结合并激活PXR的化学物质中包括有毒胆汁酸石胆酸；PXR的激活反过来可预防由这种胆汁酸引起的严重肝损伤。因此，PXR作为石胆酸以及或许其他胆汁酸的生理传感器，并协调调节参与其解毒的基因。有趣的是，抗生素利福平和草药抗抑郁药圣约翰草都可激活PXR并具有抗胆汁淤积特性，这表明更强效、更具选择性的PXR激动剂可能对治疗胆汁淤积或其他以胆汁酸或其他毒素在肝脏中蓄积为特征的疾病有用。
