Estrogen receptors as targets for drug development for breast cancer, osteoporosis and cardiovascular diseases.
Estrogen receptors as targets for drug development for breast cancer, osteoporosis and cardiovascular diseases.
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DOI：
10.2174/1568009043332880
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发表时间：
2004-08
影响因子：
3
通讯作者：
Thresia Thomas;M. Gallo;T. Thomas
中科院分区：
文献类型：
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作者：
Thresia Thomas;M. Gallo;T. Thomas
雌激素受体（ER）是介导雌二醇和一系列模拟雌二醇结构的天然和合成化学物质作用的蛋白质。雌激素作用最初归因于一种单一类型的ER，现在称为ER α，但ER β是在1995年发现的。这些蛋白质的组织特异性分布和表达强度决定了组织对雌激素化合物的第一反应。雌激素和雌激素受体在乳腺癌的发生和发展中起着重要作用，阻断雌激素受体功能的抗雌激素药物可用于乳腺癌的预防和治疗。然而，雌激素模拟物不属于激动剂和拮抗剂的不同类别，因为它们的作用是由称为辅激活子或辅抑制子的许多辅助蛋白的组织特异性表达调节的。此外，小分子如多胺、脂肪酸和硫氧还蛋白可调节ER功能。雌激素的功能包括多个器官系统，包括生殖、骨骼、心血管和神经系统。雌激素对骨重塑和矿化至关重要，因此雌激素替代疗法被证明可以加强绝经后妇女的骨健康。理想情况下，选择性阻断乳腺上皮细胞中的ER功能应该伴随着对骨和心血管系统的生长支持。为了更好地利用选择性雌激素受体调节剂（SERM），不仅可以对抗乳腺癌，还可以对抗骨质疏松症和心血管疾病，需要充分了解不同器官中雌激素功能的细节。目前对SERM的研究指出，通过利用ER作为对抗多种疾病的通用靶标来实现这一目标。
Estrogen receptors (ERs) are proteins that mediate the action of estradiol and a series of natural and synthetic chemicals that mimic the estradiol structure. Estrogenic action was initially attributed to a single type of ER, now known as ERalpha, but ERbeta was discovered in 1995. Tissue specific distribution and the intensity of expression of these proteins determine the first response of tissues to estrogenic compounds. Estrogens and ERs play a major role in the origin and progression of breast cancer, and antiestrogens that block ER function are useful for breast cancer prevention and treatment. Estrogen mimetics, however, do not fall into distinct categories of agonists and antagonists, since their action is regulated by tissue-specific expression of a number of auxiliary proteins called coactivators or corepressors. In addition, small molecules such as polyamines, fattyacids, and thioredoxin may modulate ER function. Estrogenic functions encompass multiple organ systems, including the reproductive, skeletal, cardiovascular, and nervous system. Estrogens are critical for bone remodeling and mineralization so that estrogen replacement therapy is proven to strengthen bone health in post-menopausal women. Ideally, selective blockade of ER function in breast epithelial cells should be accompanied by growth support on bone and cardiovascular systems. The details of estrogenic function in different organs are to be fully realized, in order to better utilize selective estrogen receptor modulators (SERMs) to fight not only breast cancer but also osteoporosis and cardiovascular diseases. Current research on SERMs points toward accomplishing this goal by exploiting ER as a versatile target against multiple diseases.