Expression of oestrogen receptors α and β during the period of uterine receptivity in rat:: effect of ormeloxifene, a selective oestrogen receptor modulator
Expression of oestrogen receptors α and β during the period of uterine receptivity in rat:: effect of ormeloxifene, a selective oestrogen receptor modulator
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DOI：
10.1111/j.1748-1716.2006.01638.x
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Dwivedi, A.
中科院分区：
文献类型：
--
作者：
Awasthi, S.;Blesson, C. S.;Dwivedi, A.
目的：研究雌激素受体(ER)α和β在大鼠子宫容受期的表达、分布和调节，以及奥美洛昔芬(Orm)对其的调节作用，以探讨其在子宫内膜敏化中的作用。方法：对照组和奥美洛昔芬(Orm)组大鼠分别于产后第3、4、5、5天采集子宫组织，分别为非接受期、前接受期和接受期。RT-PCR法和Western印迹法分别检测mRNA和蛋白质的表达水平。结果：逆转录-聚合酶链式反应显示ERαmRNA在第5天早晨达到高峰，而ERβmRNA表达水平很低。Orm组大鼠ERαmRNA在第5天受到抑制，第3天后ERα蛋白表达增强，ERβ蛋白表达在植入前一直很低，Orm在第5天早晨引起ERα蛋白表达下降。在子宫内膜中，ERα在子宫腔上皮、腺上皮和间质中的表达有差异。在第4天和第5天，ORM引起所有三个子宫内膜室ERα阳性核的百分比下降，减少的幅度在时空上是不同的。在ERβ的情况下，Orm处理组和对照组均未检测到免疫染色。结论：子宫对着床的复杂反应似乎是由细胞特异性ERα的不同表达决定的。研究提示，Orm在子宫容受期对ERα有抑制作用。
Aims: In the present study, we investigated expression, distribution and regulation of oestrogen receptors (ERs) alpha and beta and their modulation by ormeloxifene (Orm) during the period of uterine receptivity in rat uterus in order to determine their role in endometrial sensitization.Methods: Uterine tissues of control and Orm-treated (1.25 mg kg(-1), orally) rats were collected on days 3, 4, 5 morning and day 5 evening post-coitum referring to non-receptive, pre-receptive and receptive phases respectively. mRNA and protein expression levels were determined by RT-PCR and Western blot respectively. Immunohistochemical technique was used to localize the receptors.Results: RT-PCR analysis revealed that ER alpha mRNA reached a peak level on day 5 morning whereas ER beta mRNA expression was found to be very low. In Orm-treated rats, the ER alpha mRNA was suppressed at day 5. The protein expression of ER alpha increased after day 3 and that of ER beta remained very low throughout the pre-implantation period; Orm caused a decrease in ER alpha on day 5 morning. In endometrium, ER alpha expression was regulated differentially in luminal epithelium, glandular epithelium and stroma. Orm caused a decrease in the percentage of ER alpha-positive nuclei in all the three endometrial compartments on days 4 and 5, and the magnitude of reduction varied spatio-temporally. In case of ER beta, immunostaining was not detectable in Orm-treated and control groups.Conclusion: It appears that the complex uterine response to implantation is governed by differential cell-specific ER alpha expression. The study suggested the inhibitory activity of Orm on ER alpha during the period of uterine receptivity.