In vitro-assessment of putative antiprogestin activities of phytochemicals and synthetic UV absorbers in human endometrial Ishikawa cells
In vitro-assessment of putative antiprogestin activities of phytochemicals and synthetic UV absorbers in human endometrial Ishikawa cells
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DOI：
10.3109/09513590.2015.1047448
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发表时间：
2015-01-01
影响因子：
2
通讯作者：
Schaefer, Wolfgang R.
中科院分区：
文献类型：
--
作者：
Yin, Qinan;Fischer, Lara;Schaefer, Wolfgang R.
胚胎着床的关键步骤由黄体酮控制。这些过程可被黄体酮受体（PR）拮抗剂中断，例如用于流产的药物。天然化合物和环境化学物质诱导的抗黄体酮效应很少得到解决。在体外实验中，我们研究了植物化合物芹菜素（API）和反式阿威酸（t-FA）以及紫外线吸收剂辛烷基甲氧基肉桂酸（OMC）和4-甲基苄基樟脑（4-MBC）的抗黄体酮活性。将它们与选择性孕激素受体调节剂（SPRMs）米非司酮（RU486）和醋酸乌利司林（UPA）以及全pr拮抗剂ZK137316进行比较。采用RT-qPCR方法，通过s型浓度-响应曲线表征化合物与黄体酮联用对黄体酮敏感靶基因雌激素硫转移酶（SULT1E1）的影响。黄体酮对SULT1E1 mRNA水平的拮抗作用可被RU486、UPA和ZK137316以及芹菜素（效价较低）以浓度依赖性拮抗。t-FA、OMC和4-MBC对SULT1E1 mRNA水平无影响。我们证明，在该模型中，尽管芹菜素的浓度更高，但其效果与表征良好的SPRMs RU486和UPA或黄体酮拮抗剂ZK137316相似。我们的子宫内膜特异性石川细胞测定法是人工转激活测定法的有益补充，用于鉴定具有抗黄体酮活性的环境物质。
Critical steps of embryo implantation are controlled by progesterone. These processes can be interrupted by progesterone receptor (PR) antagonists, e.g. drugs used for abortion. Antiprogestin effects induced by natural compounds and environmental chemicals have been rarely addressed. In our in vitro study, we investigated putative antiprogestin activities of the plant compounds apigenin (API) and trans-ferulic acid (t-FA) as well as the UV absorbers octyl methoxycinnamate (OMC) and 4-methylbenzylidene camphor (4-MBC). They were compared with the selective progesterone receptor modulators (SPRMs) mifepristone (RU486) and ulipristal acetate (UPA) as well as the full PR-antagonist ZK137316. Effects of test compounds in combination with progesterone on the progesterone-sensitive target gene estrogen sulfotransferase (SULT1E1) were characterized by sigmoidal concentration-response curves obtained by RT-qPCR. The agonistic effect of progesterone on SULT1E1 mRNA levels was concentration-dependently antagonized by RU486, UPA and ZK137316 as well as, with lower potency, apigenin. t-FA, OMC and 4-MBC had no effect on SULT1E1 mRNA levels. We demonstrated that apigenin, although at higher concentrations, exerts a similar effect as the well-characterized SPRMs RU486 and UPA or the progesterone antagonist ZK137316 in this model. Our endometrium-specific Ishikawa cell assay is a useful complement to artificial transactivation assays for the identification of environmental substances with antiprogestin activities.