Progestins, progesterone receptor modulators, and progesterone antagonists change VEGF release of endometrial cells in culture
Progestins, progesterone receptor modulators, and progesterone antagonists change VEGF release of endometrial cells in culture
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DOI：
10.1016/s0039-128x(00)00180-x
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发表时间：
2000-10-01
期刊：
影响因子：
2.7
通讯作者：
Beier, HM
中科院分区：
文献类型：
--
作者：
Classen-Linke, I;Alfer, J;Beier, HM
本实验研究了合成的孕激素、醋酸甲羟孕酮（MPA）、孕激素受体调节剂J867和拮抗剂ZK 137316对离体子宫内膜上皮细胞和子宫内膜成纤维细胞的影响。我们通过RT-PCR检测了雌激素受体α（ER）和孕激素受体（PR）的表达。10（-8）M 17 β-雌二醇（E-2）处理后，成纤维细胞和上皮细胞中ER和PR表达增强。与10-6 M MPA处理相比，10 - 6 M J867或ZK 137316处理如E-2一样上调PR表达，这导致上皮细胞中PR下调，但在成纤维细胞中不下调。此外，通过VEGF-ELISA分析血管内皮生长因子（VEGF）释放到细胞培养基中。VEGF在血管生成中起重要作用，受类固醇激素和缺氧的调节。在两种细胞类型中，E-2刺激VEGF释放到培养基中，MPA在成纤维细胞培养中显著降低VEGF释放，但在上皮细胞培养中增加VEGF释放。ZK137316。在存在或不存在E-2的情况下，减少成纤维细胞培养物中VEGF的释放。J867仅在E-2存在下增加成纤维细胞中的VEGF产生。与E-2相比，这两种化合物在上皮细胞培养中均未显示出显著作用。上皮细胞和成纤维细胞的不同结果表明，PR调节剂（PRM）和孕酮拮抗剂（PA）的药理作用可能是细胞特异性的，并取决于部分孕激素激动活性的存在或不存在。这一观察结果为各种临床应用开辟了新的前景。(C)2000 Elsevier Science Inc. All rights reserved.
The influences of the synthetic progestin, medroxyprogesterone acetate (MPA), the progesterone receptor modulator J867, and the antagonist ZK137316 were studied in vitro on isolated endometrial epithelial cells, as well as endometrial fibroblasts. We evaluated the expression of estrogen receptor alpha (ER) and the progesterone receptor (PR) by RT-PCR. ER and PR were strongly expressed in the fibroblasts and epithelial cells under treatment with 10(-8) M 17 beta -estradiol (E-2). Treatment with 10(-6) M J867 or ZK137316 upregulated the PR expression as did E-2 in contrast to treatment with 10-6 M MPA, which caused a downregulation of PR in epithelial cells, but not in fibroblasts. In addition, the vascular endothelial growth factor (VEGF) release into the cell culture medium was analyzed by a VEGF-ELISA. VEGF which plays an important role in angiogenesis, is regulated by steroid hormones as well as hypoxia. E-2 stimulates VEGF release into the medium in both cell types, MPA reduces VEGF release significantly in the fibroblast cell culture, but increases it in the epithelial cell culture. ZK137316. in the presence or absence of E-2, reduces VEGF release in fibroblast cell culture. J867 increases the VEGF production in fibroblasts only in the presence of E-2. Both compounds show no significant effects, compared to E-2, in epithelial cell culture. The different results for the epithelial cells and fibroblasts indicate that the pharmacological effects of PR modulators (PRMs) and progesterone antagonists (PAs) may be cell specific and depend on the presence or absence of partial progestagenic agonistic activities. This observation opens up new perspectives for various clinical applications. (C) 2000 Elsevier Science Inc. All rights reserved.