PDF(Pubmed)
Abstract：
Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo.
摘要：
子宫内膜异位症的特征是子宫外子宫内膜样组织的生长，它与激素受体表达和炎症的改变有关。雌四醇（E4）是一种弱雌激素，最近已被批准用于避孕。我们评估了E4对子宫内膜异位症样病变生长和TNF-α表达的影响。雌激素受体（ER），和体内鼠模型中的孕酮受体(PRs)。在雌性C57BL/6小鼠中手术诱导子宫内膜异位症。E4从术后第15天通过Alzet泵(3mg/kg/天)递送,持续4周。E4显著降低异位病变的体积(p<0.001)和重量(p<0.05)。组织学上,E4不影响细胞增殖（PCNA免疫组织化学），但确实增加了细胞凋亡（TUNEL测定）（p<0.05）。此外，它调节氧化应激(SOD，CAT,和GPX活性，p<0.05)和增加的脂质过氧化(TBARS/MDA，p<0.01)。分子分析显示TNF-α的mRNA（RT-qPCR）和蛋白（ELISA）表达降低（p<0.05），Esr2的mRNA表达降低（p<0.05）。与Esr1（p<0.01）和Pgr（p<0.05）的表达增加相反。本研究首次证明E4限制了子宫内膜异位症在体内的发展和进展。
