Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA. michihisa.umetani@utsouthwestern
Trends Endocrinol Metab. 2011 Apr;22(4):130-5. doi: 10.1016/j.tem.2011.01.003. Epub 2011 Feb 23.
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.
胆固醇代谢产物 27-羟胆固醇（27OHC）经典地将固醇从外周组织递送至肝脏，并且是胆汁酸合成的底物。最近的研究表明，27OHC 还与雌激素受体 ERα 和 ERβ结合并修饰其功能。在缺乏合成 27OHC 的酶 CYP27A1 或分解 27OHC 的酶 CYP7B1 的小鼠的实验中，已经证明 27OHC 对雌激素相关的心血管保护和骨矿化有不利影响。在乳腺癌细胞中的研究进一步表明，27OHC 改变 ER 靶基因表达以促进细胞生长。因此，27OHC 是第一个被鉴定的内源性选择性雌激素受体调节剂（SERM），可能对心血管系统、骨生物学和癌症有重要影响。
