Iyer Manisha, Reschly Erica J, Krasowski Matthew D
Department of Pathology, University of Pittsburgh, Scaife Hall S-730, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Expert Opin Drug Metab Toxicol. 2006 Jun;2(3):381-97. doi: 10.1517/17425255.2.3.381.
The pregnane X receptor (PXR; NR1I2) is a nuclear hormone receptor (NR) that transcriptionally regulates genes encoding transporters and drug-metabolising enzymes in the liver and intestine. PXR activation leads to enhanced metabolism and elimination of xenobiotics and endogenous compounds such as hormones and bile salts. Relative to other vertebrate NRs, PXR has the broadest specificity for ligand activators by virtue of a large, flexible ligand-binding cavity. In addition, PXR has the most extensive sequence diversity across vertebrate species in the ligand-binding domain of any NR, with significant pharmacological differences between human and rodent PXRs, and especially marked divergence between mammalian and nonmammalian PXRs. The unusual properties of PXR complicate the use of in silico and animal models to predict in vivo human PXR pharmacology. Research into the evolutionary history of the PXR gene has also provided insight into the function of PXR in humans and other animals.
孕烷X受体（PXR；NR1I2）是一种核激素受体（NR），可转录调控肝脏和肠道中编码转运蛋白和药物代谢酶的基因。PXR激活会增强外源性物质以及激素和胆汁盐等内源性化合物的代谢和消除。相对于其他脊椎动物NR，由于具有一个大的、灵活的配体结合腔，PXR对配体激活剂具有最广泛的特异性。此外，在所有NR的配体结合域中，PXR在脊椎动物物种间具有最广泛的序列多样性，人类和啮齿动物PXR之间存在显著的药理学差异，哺乳动物和非哺乳动物PXR之间的差异尤为明显。PXR的这些特殊性质使得利用计算机模拟和动物模型预测体内人类PXR药理学变得复杂。对PXR基因进化史的研究也为了解PXR在人类和其他动物中的功能提供了线索。
