Estrogen Metabolite Ratios and Risk Assessment of Hormone‐related Cancers
Estrogen Metabolite Ratios and Risk Assessment of Hormone‐related Cancers
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雌激素代谢比率和激素相关癌症的风险评估
DOI：
10.1111/j.1749-6632.1995.tb12149.x
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发表时间：
1995
影响因子：
5.2
通讯作者：
Jay A. Fishman
中科院分区：
文献类型：
--
作者：
D. Sepkovic;Bradlow Hl;G. Ho;S. Hankinson;L. Gong;M. P. Osborne;Jay A. Fishman
雌激素被认为在乳腺恶性肿瘤中起启动/促进作用，导致转化细胞的生长速度增加。雌二醇的主要代谢产物是在C-2或C-16a位置羟基化的产物，在C-4位置的量要小得多。C-2代谢物代表雌二醇不可逆的生物转化为基本上不具有外周雌激素活性的化合物。C-2和C-16a羟基化是竞争性的替代品，这两种氧化途径之一的活性增加将导致通过替代途径形成的代谢物减少。*人体内主要的C-2代谢产物是2-羟孕酮（2-OHE1）。最近的研究表明，2-OHE是弱抗致生的。雌二醇代谢的另一个主要途径，C-16a羟基化，导致16a-羟甾酮（16a-OHE1）和雌三醇（E3）的形成。这两种化合物都具有显著的雌激素激动剂活性。16a-OHE1是一种独特的反应性雌激素，已知在人体中存在的水平与游离e~tradiol相当。~这种雌二醇代谢物能够与雌激素受体、核组蛋白和其他含氨基化合物共价结合。-7在乳腺癌妇女、乳腺癌高危妇女和自发性乳腺肿瘤高发小鼠品系中，16a-OHE1的形成水平升高。在本研究中，我们利用酶联免疫分析法检测这些代谢物
Estrogens are believed to act as initiators/promoters in breast malignancies causing increased growth rates in transformed cells. The major metabolites of estradiol are those hydroxylated at either the C-2 or C-16a positions, with a much smaller amount at the C-4 position. C-2 metabolites represent the irreversible biotransformation of estradiol to compounds that are essentially devoid of peripheral estrogenic activity.' C-2 and C-16a hydroxylation are competitive alternatives and increases in the activity of one of these two oxidative pathways will result in a diminution of metabolites formed via the alternative pathway.* The principal C-2 metabolite in humans is 2-hydroxyestrone (2-OHE1). Recent studies have shown that 2-OHE, is weakly antie~trogenic.~ The other major pathway of estradiol metabolism, C-16a hydroxylation, results in the formation of 16a-hydroxyestrone (16a-OHE1) and estriol (E3). Both of these compounds retain significant estrogen agonist activity. 16a-OHE1 is a uniquely reactive estrogen that is known to be present in humans at levels that are comparable to free e~tradiol.~ This estradiol metabolite is capable of covalently binding to estrogen receptors, to nuclear histone proteins, and to other amino-containing compounds?-7 The formation of 16a-OHE1 is elevated in women with breast cancer, in women at high risk for breast cancer, and in strains of mice with a high incidence of spontaneous mammary tumors.&l0 In the present study, we utilize an enzyme-linked immunoassay for these metabolites
影响因子：
9.3
作者：
S. Hankinson;Stephanie J. London;Christopher G. Chute;Robert L. Barbieri;Loring Jones;L. Kaplan;Frank M. Sacks;M. Stampfer
通讯作者：
S. Hankinson;Stephanie J. London;Christopher G. Chute;Robert L. Barbieri;Loring Jones;L. Kaplan;Frank M. Sacks;M. Stampfer