TY - JOUR
T1 - 27-Hydroxycholesterol
T2 - The first identified endogenous SERM
AU - Umetani, Michihisa
AU - Shaul, Philip W.
N1 - Funding Information:
The authors thank their colleagues and collaborators who have made important contributions to our understanding of the biology of 27OHC, both in cholesterol and bile acid homeostasis and as a SERM. These include David Mangelsdorf and David Russell at University of Texas Southwestern, and Carolyn DuSell and Donald McDonnell at Duke University Medical Center. This work was supported by National Institutes of Health grants DK079328 (MU) and HL087564 (PS).
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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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U2 - 10.1016/j.tem.2011.01.003
DO - 10.1016/j.tem.2011.01.003
M3 - Review article
C2 - 21353593
AN - SCOPUS:79953160837
SN - 1043-2760
VL - 22
SP - 130
EP - 135
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 4
ER -