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Trends Endocrinol Metab. 2011 Apr;22(4):130-5. doi: 10.1016/j.tem.2011.01.003. Epub 2011 Feb 23.

27-Hydroxycholesterol: the first identified endogenous SERM.

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  • 1Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA. michihisa.umetani@utsouthwestern


The cholesterol metabolite 27-hydroxycholesterol (27OHC) classically delivers sterols from peripheral tissues to the liver and is a substrate for bile acid synthesis. Recent studies have revealed that 27OHC also binds to and modifies the function of estrogen receptors ERα and ERβ. Experiments in mice lacking the enzyme which synthesizes 27OHC, CYP27A1, or the enzyme which catabolizes 27OHC, CYP7B1, have demonstrated that 27OHC adversely affects estrogen-related cardiovascular protection and bone mineralization. Work in breast cancer cells further indicates that 27OHC alters ER target gene expression to promote cell growth. Therefore, 27OHC is the first identified endogenous selective estrogen receptor modulator (SERM) and could have an important impact upon the cardiovascular system, bone biology, and cancer.

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