Biological actions of 27-hydroxycholesterol (27HC), the first identified selective estrogen receptor modulator (SERM)

In collaboration with the Mangelsdorf Laboratory here at UT Southwestern, we discovered that the cholesterol metabolite, 27-hydroxycholesterol (27HC), which is prevalent in atherosclerotic lesions, causes potent direct modulation of both plasma membrane-associated and nuclear ER function. Using pharmacologic strategies and genetic deletion of the enzyme CYP7B1 that metabolizes 27HC, we are performing experiments in mice to test the novel hypothesis that 27HC antagonizes the cardiovascular protection afforded by estrogen. These include the robust ability of estrogen to attenuate neointima formation following arterial injury.  Studies of the role of 27HC in breast cancer progression are also under way using mouse models.  The ultimate goal is to determine if 27HC abundance or action can be manipulated to enhance the ability of estrogen to prevent cardiovascular disease, or to retard breast cancer growth. 

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