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雌性Wistar大鼠雌激素敏感组织对出生前和出生后异黄酮暴露的反应。

Responses of estrogen sensitive tissues in female Wistar rats to pre- and postnatal isoflavone exposure.

作者信息

Hertrampf T, Ledwig C, Kulling S, Molzberger A, Möller F J, Zierau O, Vollmer G, Moors S, Degen G H, Diel P

机构信息

Institut für Kreislaufforschung und Sportmedizin, Abt. molekulare und zelluläre Sportmedizin, Deutsche Sporthochschule Köln, Cologne, Germany.

出版信息

Toxicol Lett. 2009 Dec 15;191(2-3):181-8. doi: 10.1016/j.toxlet.2009.08.019. Epub 2009 Sep 4.

DOI:10.1016/j.toxlet.2009.08.019
PMID:19733640
Abstract

Effects of isoflavones on estrogen sensitive tissues are discussed controversially. This study was designed to investigate tissue specific effects of an isoflavone exposure through different periods of life in female Wistar rats and to compare the effects of genistein (GEN) to those of mixed dietary isoflavones, GEN and daidzein (DAI). One group received an isoflavone-free diet (IDD), another was fed an isoflavone-rich diet (IRD) and the third group an IDD supplemented with GEN (GEN(d)) prior to mating, throughout pregnancy and up to weaning. The offspring were kept on the respective diets during growth, puberty and adulthood. The weight of the uterus, the height of the uterine and vaginal epithelium, the bone mineral density of the tibia, and the expression of the estrogen sensitive gene CaBP9K in the liver were determined. At d21, the uterine weight, the uterine epithelium and the expression of CaBP9K in the liver were significantly stimulated in GEN(d) animals compared to IDD and IRD. Interestingly, bone mineral density was increased in GEN(d) and in IRD animals. Around puberty (d50) neither uterine wet weights nor trabecular bone density differed significantly among the isoflavone groups and the IDD control. At d80 no significant differences in uterine weight were observed among IDD, GEN(d) and IRD animals. However, bone mineral density was increased in GEN(d) and IRD animals. In summary, our results demonstrate that lifelong dietary exposure to isoflavones can affect estrogen sensitive tissues, apparently in a tissue selective manner. With respect to health risk and benefit our data indicate that an increased bone mineral density can be achieved by lifelong exposure to an IRD, which, in contrast to GEN supplementation, does not seem to stimulate the proliferation of the uterine epithelium.

摘要

异黄酮对雌激素敏感组织的影响存在争议。本研究旨在调查雌性Wistar大鼠在不同生命阶段暴露于异黄酮的组织特异性影响,并比较染料木黄酮(GEN)与混合膳食异黄酮、GEN和大豆苷元(DAI)的影响。一组接受无异黄酮饮食(IDD),另一组喂食富含异黄酮的饮食(IRD),第三组在交配前、整个孕期直至断奶期间接受添加GEN的IDD(GEN(d))。后代在生长、青春期和成年期保持各自的饮食。测定子宫重量、子宫和阴道上皮高度、胫骨骨矿物质密度以及肝脏中雌激素敏感基因CaBP9K的表达。在第21天,与IDD和IRD相比,GEN(d)组动物的子宫重量、子宫上皮以及肝脏中CaBP9K的表达受到显著刺激。有趣的是,GEN(d)组和IRD组动物的骨矿物质密度增加。在青春期前后(第50天),异黄酮组和IDD对照组之间的子宫湿重和小梁骨密度均无显著差异。在第80天,IDD、GEN(d)和IRD组动物的子宫重量未观察到显著差异。然而,GEN(d)组和IRD组动物的骨矿物质密度增加。总之,我们的结果表明,终身饮食暴露于异黄酮可影响雌激素敏感组织,显然是以组织选择性的方式。关于健康风险和益处,我们的数据表明,终身暴露于IRD可提高骨矿物质密度,与补充GEN相比,IRD似乎不会刺激子宫上皮细胞增殖。

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