27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator.

27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator.
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DOI:
10.1016/j.maturitas.2017.07.014
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发表时间:
2017-10
期刊:
影响因子:
4.9
通讯作者:
Nelson ER
Nelson ER
中科院分区:
医学2区
文献类型:
--
作者:
He S;Nelson ER

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雌激素受体(ER)介导甾体雌激素的作用,并且对于几种生理和病理生理过程的调节是重要的,包括生殖、骨生理、心血管生理和乳腺癌。ER的独特药理学允许某些配体,如他莫昔芬,引发组织和环境特异性反应,配体现在被称为选择性雌激素受体调节剂(SERM)。最近,胆固醇代谢产物27-羟基胆固醇(27 HC)已被定义为内源性SERM,在动脉粥样硬化、骨质疏松症、乳腺癌和前列腺癌以及神经退行性疾病中具有活性。由于27 HC浓度与胆固醇浓度密切相关,因此27 HC可能介导胆固醇的许多生物学效应。本文概述了ER药理学,并总结了迄今为止的工作涉及27 HC在各种疾病。只要有可能,我们强调临床数据,以支持27 HC在所讨论的疾病中的作用。
Estrogen receptors (ERs) mediate the actions of the steroidal estrogens, and are important for the regulation of several physiological and pathophysiological processes, including reproduction, bone physiology, cardiovascular physiology and breast cancer. The unique pharmacology of the ERs allows for certain ligands, such as tamoxifen, to elicit tissue- and context-specific responses, ligands now referred to as selective estrogen receptor modulators (SERMs). Recently, the cholesterol metabolite 27-hydroxychoelsterol (27HC) has been defined as an endogenous SERM, with activities in atherosclerosis, osteoporosis, breast and prostate cancers, and neural degenerative diseases. Since 27HC concentrations closely mirror those of cholesterol, it is possible that 27HC mediates many of the biological effects of cholesterol. This paper provides an overview of ER pharmacology and summarizes the work to date implicating 27HC in various diseases. Wherever possible, we highlight clinical data in support of a role for 27HC in the diseases discussed.
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