Kliewer S A, Moore J T, Wade L, Staudinger J L, Watson M A, Jones S A, McKee D D, Oliver B B, Willson T M, Zetterström R H, Perlmann T, Lehmann J M
Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA.
Cell. 1998 Jan 9;92(1):73-82. doi: 10.1016/s0092-8674(00)80900-9.
Steroid hormones exert profound effects on differentiation, development, and homeostasis in higher eukaryotes through interactions with nuclear receptors. We describe a novel orphan nuclear receptor, termed the pregnane X receptor (PXR), that is activated by naturally occurring steroids such as pregnenolone and progesterone, and synthetic glucocorticoids and antiglucocorticoids. PXR exists as two isoforms, PXR.1 and PXR.2, that are differentially activated by steroids. Notably, PXR.1 is efficaciously activated by pregnenolone 16alpha-carbonitrile, a glucocorticoid receptor antagonist that induces the expression of the CYP3A family of steroid hydroxylases and modulates sterol and bile acid biosynthesis in vivo. Our results provide evidence for the existence of a novel steroid hormone signaling pathway with potential implications in the regulation of steroid hormone and sterol homeostasis.
类固醇激素通过与核受体相互作用，对高等真核生物的分化、发育和体内平衡产生深远影响。我们描述了一种新型孤儿核受体，称为孕烷X受体（PXR），它可被天然存在的类固醇如孕烯醇酮和孕酮以及合成糖皮质激素和抗糖皮质激素激活。PXR以两种异构体PXR.1和PXR.2的形式存在，它们被类固醇差异激活。值得注意的是，PXR.1可被孕烯醇酮16α-腈有效激活，孕烯醇酮16α-腈是一种糖皮质激素受体拮抗剂，可诱导类固醇羟化酶CYP3A家族的表达，并在体内调节固醇和胆汁酸的生物合成。我们的结果为存在一种新型类固醇激素信号通路提供了证据，该通路可能对类固醇激素和固醇体内平衡的调节有影响。
