Lehmann J M, Kliewer S A, Moore L B, Smith-Oliver T A, Oliver B B, Su J L, Sundseth S S, Winegar D A, Blanchard D E, Spencer T A, Willson T M
Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA.
J Biol Chem. 1997 Feb 7;272(6):3137-40. doi: 10.1074/jbc.272.6.3137.
Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7alpha-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRalpha and LXRbeta, two orphan members of the nuclear receptor superfamily, are activated by 24(S), 25-epoxycholesterol and 24(S)-hydroxycholesterol at physiologic concentrations. In addition, we have identified an LXR response element in the promoter region of the rat cholesterol 7alpha-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXRs play a critical role in the regulation of cholesterol homeostasis.
胆固醇的积累既会抑制控制胆固醇生物合成和细胞摄取的基因，又会诱导胆固醇7α-羟化酶，从而通过增加代谢为胆汁酸来清除胆固醇。在此，我们报告核受体超家族的两个孤儿成员LXRα和LXRβ在生理浓度下被24(S), 25-环氧胆固醇和24(S)-羟基胆固醇激活。此外，我们在大鼠胆固醇7α-羟化酶基因的启动子区域鉴定出一个LXR反应元件。我们的数据为一种新的激素信号通路提供了证据，该通路响应氧化固醇激活转录，并表明LXRs在胆固醇稳态调节中起关键作用。
