Regulation of the estrogen receptor and its messenger ribonucleic acid in the ovariectomized sheep myometrium and endometrium: the role of estradiol and progesterone.
Regulation of the estrogen receptor and its messenger ribonucleic acid in the ovariectomized sheep myometrium and endometrium: the role of estradiol and progesterone.
复制标题
去势羊子宫肌层和子宫内膜中雌激素受体及其信使核糖核酸的调节：雌二醇和黄体酮的作用。
DOI：
10.1095/biolreprod55.4.762
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发表时间：
1996
影响因子：
3.6
通讯作者：
Nathanielsz,PW
中科院分区：
文献类型：
--
作者：
Wu,WX;Owiny,J;Zhang,Q;Ma,XH;Nathanielsz,PW
在糖皮质激素诱导的早产和足月自然分娩过程中，绵羊子宫肌层和子宫内膜中雌激素受体(ER)基因的表达显著增加。然而，分娩过程中子宫ER上调的潜在机制仍不清楚。本研究以去卵巢(OVX)的未孕绵羊为研究对象，分析了雌二醇和孕酮在体内对子宫肌层和子宫内膜ER蛋白和ER mRNA的调节作用。将21只去卵巢母羊随机分为生理盐水组(n=6)和雌二醇组(n=6)。用孕酮海绵阴道给药2天(50μg/d，n=5)，或用孕酮海绵阴道给药10天(含孕酮0.3g，n=5)，或用孕酮海绵阴道给药10天，在第9天和第10天给予雌二醇(50μg/d)，同时孕酮海绵仍在原地(n=5)。Western印迹分析显示，雌二醇处理后，子宫肌层胞浆和胞核ER蛋白浓度显著增加(p<；0.05)，而单独使用孕酮对ER水平无明显影响。ER蛋白升高仅见于子宫内膜的核部分。然而，当雌二醇与孕酮联合应用时，孕酮可拮抗雌二醇对子宫内膜和子宫肌层ER水平的上调作用。细胞ER mRNA的变化遵循ER蛋白水平观察到的模式。雌激素受体mRNA只有在雌二醇组显著升高(p<；0.01)。孕酮单独作用和孕酮与雌二醇联合作用的母羊ER基因的表达与对照组相似。这些观察结果表明，非妊娠绵羊子宫肌层和子宫内膜中ER基因的表达和ER合成的活跃是雌激素依赖的。黄体酮可以拮抗这种雌激素作用。孕酮与雌二醇联用可下调雌激素受体基因的表达。原位杂交结果显示，ER mRNA均匀分布于子宫肌层的平滑肌细胞、血管及子宫内膜腺上皮细胞。综上所述，我们观察到非妊娠绵羊子宫肌层和子宫内膜中雌激素依赖的ER基因表达的激活以及ER合成的活跃。孕酮作为雌激素的拮抗剂对ER基因的表达具有拮抗作用。
Estrogen receptor (ER) mRNA is dramatically increased in sheep myometrium and endometrium during glucocorticoid-induced premature labor and term spontaneous labor. However, the underlying mechanism for the up-regulation of uterine ER in labor is still unknown. We used ovariectomized (OVX) nonpregnant sheep to analyze the role of estradiol and progesterone in the regulation of myometrial and endometrial ER protein and ER mRNA in vivo. Twenty-one OVX ewes were treated with saline (n = 6), or with estradiol infused i.v. for 2 days (50 μg/day, n = 5), or with an intravaginal progesterone sponge for 10 days (containing 0.3 g progesterone, n = 5), or with an intravaginal progesterone sponge for 10 days with estradiol (50 μg/day) administered on Days 9 and 10 with the progesterone sponge still in place (n = 5). The ER protein concentration in both cytosolic and nuclear compartments, analyzed by Western blot, increased significantly (p< 0.05) in the myometrium after estradiol treatment, while progesterone alone had no detectable effect on ER level. Elevated ER protein was observed only in the nuclear fraction of endometrium. However, when estradiol was given together with progesterone treatment, progesterone antagonized the up-regulatory effect of estradiol on the ER level both at the endometrium and myometrium. The changes in cellular ER mRNA followed the pattern observed at the ER protein level. Estrogen receptor mRNA was elevated significantly (p< 0.01) only in estradiol-treated ewes. Expression of the ER gene in ewes receiving progesterone alone or progesterone combined with estradiol was similar to that of the control group. From these observations we conclude that ER gene expression and active ER synthesis in nonpregnant sheep myometrium and endometrium are estradiol-dependent. Progesterone antagonizes this estrogen action. Progesterone down-regulated the elevated ER mRNA when used together with estradiol. In situ hybridization showed that ER mRNA was evenly distributed in the smooth muscle cells and blood vessels of the myometrium and the epithelial cells of the glands in endometrium. In conclusion, we have observed estradiol-dependent activation of ER gene expression as well as active ER synthesis in the nonpregnant sheep myometrium and endometrium. Progesterone acted as an antagonist of estradiol on ER gene expression.