Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Studies in Reproduction, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Mol Reprod Dev. 2010 May;77(5):430-8. doi: 10.1002/mrd.21163.
Estrogen has an important role in the reconstruction of a new vascular network in the endometrium during each menstrual cycle; however, the underlying mechanisms are incompletely understood. Angiopoietin-1 (Ang-1) promotes vessel assembly, whereas Ang-2 and thrombospondin-1 (TSP-1) cause vessel breakdown. To determine the potential effect of estrogen on the expression of these angioregulatory factors in the endometrium, Ang-1, Ang-2, TSP-1, and Tie-2 receptor mRNA levels were assessed by real-time reverse transcriptase polymerase chain reaction in glandular epithelial and stromal cells isolated from the endometrium of ovariectomized baboons treated acutely with estradiol. Corresponding protein expression was assessed by immunocytochemistry and the proximity ligation assay (PLA) during advancing stages of the baboon menstrual cycle. Serum estradiol levels in ovariectomized baboons were 400 pg/ml within 4-6 hr of estradiol treatment. Ang-1 mRNA levels in glandular epithelial cells increased threefold (P < 0.01) within 4 hr of estradiol administration. In contrast, TSP-1 mRNA levels decreased four- to fivefold (P < 0.01) in endometrial glandular epithelial and stromal cells 4-6 hr after estradiol, whereas Ang-2 and Tie-2 expression was unaltered. Immunostaining for Ang-1 increased, TSP-1 decreased, and Ang-2 and Tie-2 were unaltered in the endometrium during the secretory compared with the proliferative phase of the cycle. Endometrial Ang-1 protein expression, quantified by PLA, increased 10-fold (P < 0.05) between the early proliferative and late proliferative/mid-secretory phases of the menstrual cycle in association with the rise in estrogen. In summary, estrogen induced a rapid, divergent, and cell-specific change in expression of angiostimulatory and angioinhibitory growth factors in the endometrium of the nonhuman primate.
雌激素在每个月经周期的子宫内膜新血管网络重建中起着重要作用；然而，其潜在机制尚不完全清楚。血管生成素-1（Ang-1）促进血管组装，而血管生成素-2（Ang-2）和血小板反应蛋白-1（TSP-1）则导致血管破裂。为了确定雌激素对子宫内膜中这些血管生成调节因子表达的潜在影响，通过实时逆转录聚合酶链反应（PCR）评估了从去卵巢狒狒子宫内膜中分离的腺上皮细胞和基质细胞中 Ang-1、Ang-2、TSP-1 和 Tie-2 受体 mRNA 水平，在去卵巢狒狒月经周期的进展阶段通过免疫细胞化学和接近连接分析（PLA）评估了相应的蛋白质表达。去卵巢狒狒的血清雌二醇水平在接受雌二醇治疗后 4-6 小时内达到 400pg/ml。在给予雌二醇后 4 小时内，腺上皮细胞中 Ang-1 mRNA 水平增加了三倍（P < 0.01）。相比之下，TSP-1 mRNA 水平在给予雌二醇后 4-6 小时在子宫内膜腺上皮细胞和基质细胞中减少了四到五倍（P < 0.01），而 Ang-2 和 Tie-2 的表达则没有改变。与增殖期相比，在分泌期，子宫内膜中 Ang-1 的免疫染色增加，TSP-1 减少，Ang-2 和 Tie-2 没有改变。PLA 定量的子宫内膜 Ang-1 蛋白表达在月经周期的早期增殖期和晚期增殖/中期分泌期之间增加了 10 倍（P < 0.05），与雌激素的升高有关。总之，雌激素在非人类灵长类动物的子宫内膜中诱导了一种快速、不同和细胞特异性的血管生成刺激和血管生成抑制生长因子表达的变化。
