title: Re-adopting classical nuclear receptors by cholesterol metabolites.
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.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, 3517 Cullen Blvd, SERC 545, Houston, TX 77204-5056, USA. Electronic address: mumetani@UH.edu.
authors.forename: Michihisa
authors.initials: M
authors.lastname: Umetani
mesh_terms: D000818:Animals; D015519:Bone Density; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D013261:Sterols; C076996:27-hydroxycholesterol; D002784:Cholesterol
keywords: 27-Hydroxycholesterol; Estrogen receptor; LXR; Oxysterol; SERM