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Re-adopting classical nuclear receptors by cholesterol metabolites - PubMed

Review

Re-adopting classical nuclear receptors by cholesterol metabolites

Michihisa Umetani. J Steroid Biochem Mol Biol. 2016 Mar.

Abstract

Since the first cloning of the human estrogen receptor (ER) α in 1986 and the subsequent cloning of human ERβ, there has been extensive investigation of the role of estrogen/ER. Estrogens/ER play important roles not only in sexual development and reproduction but also in a variety of other functions in multiple tissues. Selective Estrogen Receptor Modulators (SERMs) are ER lignds that act as agonists or antagonists depending on the target genes and tissues, and until recently, only synthetic SERMs have been recognized. However, the discovery of the first endogenous SERM, 27-hydroxycholesterol (27HC), opened a new dimension of ER action in health and disease. In addition to the identification of 27HC as a SERM, oxysterols have been recently demonstrated as indirect modulators of ER through interaction with the nuclear receptor Liver X Receptor (LXR) β. In this review, the recent progress on these novel roles of oxysterols in ER modulation is summarized.

Keywords: 27-Hydroxycholesterol; Estrogen receptor; LXR; Oxysterol; SERM.

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Figures

**Figure 1**
Regulation of vascular function by oxysterols, LXR and ER. In normal conditions of low cholesterol/27HC, oxysterols or LXR ligands bind to LXRβ. LXR activation stimulates the nonnuclear action of ERα, thereby increasing NO release and promoting recovery from vascular injury and vascular dilation. In hypercholesterolemia, which includes high 27HC levels, 27HC inhibits ER action and suppresses the vasoprotective effects mediated by ER. Modified from ref. .

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Re-adopting classical nuclear receptors by cholesterol metabolites - PubMed