选择性雌激素酶调节器在乳腺癌:审查。

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选择性雌激素酶调节器在乳腺癌:审查。

Biochim Biophys学报。2004年6月7日,1654 (2):123 - 43。

PubMed ID

15172700 (在PubMed

]

文摘

完善,增加接触雌二醇(E(2))是一个重要的风险因素乳房肿瘤的起源和演化,其中大部分(约95 - 97%)在他们的早期阶段时。然而,三分之二的乳腺癌发生在绝经期间当卵巢停止功能。尽管循环雌激素水平低,组织的这些激素的浓度明显高于那些在等离子体或在该地区的乳房视为正常组织,表明一个特定tumoral这些激素的生物合成和积累。几个因素可能参与这个过程,包括更高的类固醇从等离子体吸收和地方形成强有力的E(2)的乳腺癌组织本身。这个信息延伸的概念“intracrinology”,一种激素可以有相同的生物反应器官产生。乳腺癌组织中有大量信息包含所有酶负责当地流通的E(2)从生物合成前体。中涉及的两个主要途径的最后步骤E(2)形成在乳腺癌组织:将雄激素转化为雌激素的“芳香化酶通路”,和“硫酸酯酶通路”转化为雌激素酮硫酸盐(E (1) S) E estrone-sulfatase (1)。类固醇生成的最后一步是弱者的转换E(1)有效的生物活性E(2)的行动还原17 beta-hydroxysteroid脱氢酶1型活动(17 beta-hsd-1)。定量评价表明,在人类乳腺肿瘤E (1) S“通过硫酸酯酶”是一种更有可能比雄激素前体为E(2)通过芳香化酶。人类乳腺癌组织包含所有的酶(17 beta-hydroxysteroid雌激素酮硫酸酯酶、脱氢酶、芳香化酶)参与的最后步骤E(2)生物合成。 This tissue also contains sulfotransferase for the formation of the biologically inactive estrogen sulfates. In recent years, it was demonstrated that various progestins (promegestone, nomegestrol acetate, medrogestone, dydrogesterone, norelgestromin), tibolone and its metabolites, as well as other steroidal (e.g. sulfamates) and non-steroidal compounds, are potent sulfatase inhibitors. Various progestins can also block 17beta-hydroxysteroid dehydrogenase activities. In other studies, it was shown that medrogestone, nomegestrol acetate, promegestone or tibolone can stimulate the sulfotransferase activity for the local production of estrogen sulfates. All these data, in addition to numerous agents which can block the aromatase action, lead to the new concept of 'Selective Estrogen Enzyme Modulators' (SEEM) which can largely apply to breast cancer tissue. The exploration of various progestins and other active agents in trials with breast cancer patients, showing an inhibitory effect on sulfatase and 17beta-hydroxysteroid dehydrogenase, or a stimulatory effect on sulfotransferase and consequently on the levels of tissular levels of E(2), will provide a new possibility in the treatment of this disease.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Norelgestromin	Steryl-sulfatase	蛋白质	人类	未知的	抑制剂	细节