Fujimoto Nariaki, Kohta Ryuki, Kitamura Shigeyuki
Department of Developmental Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami, 734-8553, Japan.
Life Sci. 2004 Jan 30;74(11):1417-25. doi: 10.1016/j.lfs.2003.08.012.
Nordihydroguaiaretic acid (NDGA), an antioxidant which has been used to preserve oils and foods, has recently become well known as a putative anticancer agent. Although NDGA is a member of the lignan family, its hormonal activities have not been well investigated. Here we show that NDGA has in vitro estrogenic activity in the ERE-luc reporter system using NIH3T3 cells, and in the estrogen-responsive cell growth assay in a pituitary cell line, MtT/E-2. Uterotropic assay in rats indicated that NDGA has estrogenic activity in vivo as well, albeit weak. Interestingly it preferentially induced ERalpha mediated ERE-luc activity, although it showed similar binding affinity to both ERalpha and ERbeta. With ERbeta, on the other hand, NDGA showed only weak agonistic action, and antagonized the estrogenic action of 17beta-estradiol when the two were coadministered. These data suggest that NDGA is an estrogenic agonist for ERalpha : ERE transcription and a mixed agonist/antagonist for ERbeta mediated ERE transactivation.
去甲二氢愈创木酸（NDGA）是一种用于保存油脂和食品的抗氧化剂，最近作为一种潜在的抗癌药物而广为人知。尽管NDGA是木脂素家族的一员，但其激素活性尚未得到充分研究。在此我们表明，NDGA在使用NIH3T3细胞的ERE - 荧光素酶报告系统中以及在垂体细胞系MtT/E - 2的雌激素反应性细胞生长测定中具有体外雌激素活性。大鼠子宫增重试验表明，NDGA在体内也具有雌激素活性，尽管较弱。有趣的是，尽管它对ERα和ERβ显示出相似的结合亲和力，但它优先诱导ERα介导的ERE - 荧光素酶活性。另一方面，对于ERβ，NDGA仅表现出微弱的激动作用，并且当二者共同给药时，它拮抗17β - 雌二醇的雌激素作用。这些数据表明，NDGA是ERα：ERE转录的雌激素激动剂以及ERβ介导的ERE反式激活的混合激动剂/拮抗剂。
