Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking.
Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking.
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DOI：
10.1097/00006254-198708000-00017
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发表时间：
1986-11
期刊：
影响因子：
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通讯作者：
J. Michnovicz;R. Hershcopf;H. Naganuma;H. Bradlow;J. Fishman
中科院分区：
文献类型：
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作者：
J. Michnovicz;R. Hershcopf;H. Naganuma;H. Bradlow;J. Fishman
流行病学数据表明，吸烟与一种重要的抗雌激素作用有关，肝脏代谢增强被认为是可能的机制。我们检验了女性吸烟会导致雌二醇2-羟化增加的假说。这种不可逆的代谢途径产生2-羟基雌激素，具有最低限度的外周雌激素活性，并迅速从循环中清除。我们发现，每天至少抽15支烟的绝经前女性的雌二醇2-羟化水平显著增加。反应程度(平均+/-扫描电子显微镜)在14名吸烟者中为53.6%+/-2.2%，在13名不吸烟对照组中为35.1+/-1.8%，增加了约50%(P<0.001)。5名吸烟者的2-羟化程度在其月经周期的卵泡期和黄体期没有变化。此外，吸烟者尿雌三醇相对雌酮的排泄量显著减少(P<0.01)，这提供了吸烟诱导的2-羟化增加减少了涉及16α-羟化的竞争性代谢途径的证据。这项研究表明，吸烟对雌二醇代谢的2-羟化途径具有很强的诱导作用，这可能导致雌激素靶组织的生物利用度降低。阐明吸烟引起的2-羟化改变的机制可能有助于开发降低激素依赖型肿瘤风险的策略。
Epidemiologic data indicate that cigarette smoking is associated with an important anti-estrogenic effect, and increased hepatic metabolism has been suggested as a possible mechanism. We examined the hypothesis that cigarette smoking in women induces an increase in estradiol 2-hydroxylation. This irreversible metabolic pathway yields 2-hydroxyestrogens, which possess minimal peripheral estrogenic activity and are cleared rapidly from the circulation. We found a significant increase in estradiol 2-hydroxylation in premenopausal women who smoked at least 15 cigarettes per day. The extent of the reaction (mean +/- SEM) was 53.6 +/- 2.2 percent among 14 smokers and 35.1 +/- 1.8 percent among 13 nonsmoking controls--an increase of approximately 50 percent (P less than 0.001). The extent of 2-hydroxylation among five smokers did not vary during the follicular and luteal phases of their menstrual cycles. In addition, urinary excretion of estriol relative to estrone was significantly decreased among smokers (P less than 0.01), providing evidence that the smoking-induced increase in 2-hydroxylation diminishes the competing metabolic pathway involving 16 alpha-hydroxylation. This study demonstrates that smoking exerts a powerful inducing effect on the 2-hydroxylation pathway of estradiol metabolism, which is likely to lead to decreased bioavailability at estrogen target tissues. Elucidation of the mechanism responsible for smoking-induced changes in 2-hydroxylation may be useful in the development of strategies to reduce the risk of hormone-dependent tumors.