Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway

Jürgen M. Lehmann, Steven A. Kliewer, Linda B. Moore, Tracey A. Smith-Oliver, Beverly B. Oliver, Jui Lan Su, Scott S. Sundseth, Deborah A. Winegar, Daniel E. Blanchard, Thomas A. Spencer, Timothy M. Willson

Research output: Contribution to journalArticlepeer-review

967 Scopus citations

Abstract

Accumulation of cholesterol causes both repression of genes controlling cholesterol biosynthesis and cellular uptake and induction of cholesterol 7α-hydroxylase, which leads to the removal of cholesterol by increased metabolism to bile acids. Here, we report that LXRα and LXRβ, 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 7α-hydroxylase gene. Our data provide evidence for a new hormonal signaling pathway that activates transcription in response to oxysterols and suggest that LXR play a critical role in the regulation of cholesterol homeostasis.

Original languageEnglish (US)
Pages (from-to)3137-3140
Number of pages4
JournalJournal of Biological Chemistry
Volume272
Issue number6
DOIs
StatePublished - 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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