Progesterone induces the fibulin-1 expression in human endometrial stromal cells
Progesterone induces the fibulin-1 expression in human endometrial stromal cells
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DOI：
10.1093/humrep/deh841
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发表时间：
2005-06-01
影响因子：
6.1
通讯作者：
Kanzaki, H
中科院分区：
文献类型：
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作者：
Nakamoto, T;Okada, H;Kanzaki, H
背景：通过对人子宫内膜基质细胞 (ESC) 进行微阵列分析，我们之前报道了 fibulin-1（一种细胞外基质和血浆糖蛋白）的 mRNA 受到孕酮的上调。在本研究中，我们试图阐明fibulin-1在人类子宫内膜中的时空调控机制。方法和结果：对人子宫内膜组织进行实时PCR实验定量分析，发现分泌期子宫内膜的fibulin-1 mRNA表达量显着高于增殖期子宫内膜。免疫组织化学研究表明，fibulin-1 蛋白在增殖期子宫内膜的腺上皮中表达，而在分泌期子宫内膜中该表达转至基质。在 ESC 培养实验中，用 6 α-甲基-17 α-羟基孕酮醋酸盐 (MPA) 或 8 溴腺苷 3':5'-环单磷酸 (8-Br-cAMP) 处理的细胞中观察到 fibulin-1 mRNA 表达显着增加。 MPA 以剂量依赖性方式刺激 fibulin-1 mRNA 表达，而黄体酮拮抗剂 RU-486 几乎完全抑制这种刺激作用。相比之下，单独使用 β-雌二醇不会增加 fibulin-1 mRNA 的表达。结论：这些结果表明 fiblin-1 是介导人类 ESC 向着床分化过程中黄体酮作用的重要分子。
BACKGROUND: By using microarray analysis with human endometrial stromal cells (ESCs), we previously reported that the mRNA for fibulin-1, an extracellular matrix as well as a plasma glycoprotein, is up-regulated by progesterone. In the present study, we tried to clarify the spatial and temporal regulation mechanism of fibulin-1 in the human endometrium. METHODS AND RESULTS: Quantitative analysis with real-time PCR experiments on human endometrial tissues showed significantly higher fibulin-1 mRNA expressions in secretory phase endometria than in proliferative phase. Immunohistochemical studies revealed that the fibulin-1 protein is expressed in the glandular epithelium in proliferative phase endometria, and that expression switched to the stroma in secretory phase endometria. In culture experiments with ESCs, a significant increase of fibulin-1 mRNA expression was observed in cells treated with 6 alpha-methyl-17 alpha-hydroxy-progesterone acetate (MPA) or 8 bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP). MPA stimulated the fibulin-1 mRNA expression in a dose-dependent manner, and a progesterone antagonist, RU-486, inhibited the stimulatory effect almost completely. By contrast, beta-estradiol alone did not increase the fibulin-1 mRNA expression. CONCLUSIONS: These results suggest that fiblin-1 is an important molecule that mediates progesterone action in human ESC differentiation towards implantation.