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Re-adopting classical nuclear receptors by cholesterol metabolites #MMPMID26563834
Since the first cloning of the human estrogen receptor (ER) ? in 1986 and the subsequent cloning of human ER?, 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) ?. In this review, the recent progress on these novel roles of oxysterols in ER modulation is summarized.