An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway
An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway
复制标题
DOI：
10.1016/s0092-8674(00)80900-9
复制
发表时间：
1998-01-09
期刊：
影响因子：
64.5
通讯作者：
Lehmann, JM
中科院分区：
文献类型：
--
作者：
Kliewer, SA;Moore, JT;Lehmann, JM
类固醇激素通过与核受体的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的影响。我们描述了一种新的孤儿核受体，被称为双氢吡喃X受体（PXR），这是激活的天然存在的类固醇，如双氢烯醇酮和孕酮，和合成的糖皮质激素和抗糖皮质激素。PXR存在两种亚型，PXR.1和PXR.2，它们被类固醇差异激活。值得注意的是，PXR. 1可有效地被异烯醇酮16 α-甲腈激活，异烯醇酮16 α-甲腈是一种糖皮质激素受体拮抗剂，可诱导CYP 3A家族类固醇羟化酶的表达，并调节体内固醇和胆汁酸的生物合成。我们的研究结果提供了一个新的类固醇激素信号通路的存在与类固醇激素和固醇稳态的调节的潜在影响的证据。
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 16 alpha-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.