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首页> 外文期刊>Archives of Toxicology >Differential response of immature rat uterine tissue to ethinylestradiol and the red wine constituent resveratrol.
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Differential response of immature rat uterine tissue to ethinylestradiol and the red wine constituent resveratrol.

机译：未成熟大鼠子宫组织对炔雌醇和红酒成分白藜芦醇的差异反应。

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The stilbene derivative resveratrol (RES) is a phytoalexin of grapes, peanuts and other fruits. It is structurally related to stilbene estrogens and an estrogenic potential of RES has recently been demonstrated in a number of in vitro studies. In this investigation, the uterotrophic responses of immature Wistar rats to subcutaneous administration of RES (18, 58, and 575 mg/ kg) and the reference estrogen ethinylestradiol (EE2; 0.3, 1, 3, 30 microg/kg) on three consecutive days were determined. Uterine weight, histopathological changes, immunohistochemical expression of nuclear estrogen receptor-alpha (ERalpha) and progesterone receptor (PR) protein, gene expression of ERalpha and PR at the messenger ribonucleic acid (mRNA) level and peroxidase induction were examined. EE2 dose dependently increased uterine weight, enlarged the uterine lumen and induced hypertrophy of epithelial, stromal and myometrial cells. Expression of ERalpha protein in epithelial, stromal and myometrial nuclei and of PR protein in epithelial nuclei was reduced in EE2-treated rats, while PR protein in stromal and myometrial nuclei was increased in a dose-dependent manner. EE2 increased messenger ribonucleic acid (mRNA) levels of uterine PR and induced peroxidase activity. In contrast, RES rather mildly decreased uterine weight, while histology did not reveal differences between controls and RES-treated rats. Expression of nuclear ERalpha protein was dose dependently decreased in epithelial, stromal and myometrial cells of RES-treated rats, while nuclear PR protein content was similar in controls and RES-treated rats. Following administration of RES, a trend toward reduced levels of ERalpha and PR mRNA was found, while no peroxidase induction occurred. Plasma levels of RES, 45 min after the administration of a single subcutaneous dose of 500 mg/kg, were in the range 1-2 microM. In summary, an estrogenic potential of RES could not be substantiated in this in vivo study, although the most effective route of administration and extremely high doses were used and plasma levels were in the range reported to be effective in vitro. Whether other pharmacological properties of RES could mediate the observed changes in RES-treated animals is discussed.
机译：二苯乙烯衍生物白藜芦醇（RES）是葡萄，花生和其他水果的植物抗毒素。它在结构上与二苯乙烯雌激素有关，最近在许多体外研究中证实了RES的雌激素潜力。在这项研究中，未成熟的Wistar大鼠对皮下注射RES（18、58和575 mg / kg）和参考雌激素炔雌醇（EE2; 0.3、1、3、30 microg / kg）的连续三天的子宫营养反应被确定。检查子宫重量，组织病理学变化，核雌激素受体（ERalpha）和孕激素受体（PR）蛋白的免疫组织化学表达，信使核糖核酸（mRNA）水平上ERalpha和PR的基因表达以及过氧化物酶诱导。 EE2剂量依赖性地增加子宫重量，扩大子宫腔并诱导上皮，基质和子宫肌层细胞肥大。在EE2处理的大鼠中，ERalpha蛋白在上皮，间质和子宫肌层细胞核中的表达以及PR蛋白在上皮细胞核中的表达降低，而间质和肌层细胞核中的PR蛋白以剂量依赖的方式增加。 EE2增加子宫PR的信使核糖核酸（mRNA）水平并诱导过氧化物酶活性。相反，RES轻度减轻了子宫重量，而组织学未显示对照组和RES治疗的大鼠之间的差异。 RES处理的大鼠上皮，基质和肌层细胞中核ERalpha蛋白的表达呈剂量依赖性降低，而对照组和RES处理的大鼠中核PR蛋白含量相似。服用RES后，发现ERalpha和PR mRNA水平降低的趋势，而未发生过氧化物酶诱导。皮下注射500 mg / kg单一剂量后45分钟，RES的血浆水平为1-2 microM。总而言之，尽管使用了最有效的给药途径和极高的剂量，并且血浆水平在体外有效范围内，但在这项体内研究中无法证实RES的雌激素潜力。讨论了RES的其他药理性质是否可以介导在RES治疗的动物中观察到的变化。

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