The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells

The orphan nuclear receptor Nur77 regulates decidual prolactin expression in human endometrial stromal cells
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孤儿核受体Nur77调节人子宫内膜基质细胞中蜕膜催乳素的表达

DOI:
10.1016/j.bbrc.2010.12.027
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发表时间:
2011-01-14
影响因子:
3.1
通讯作者:
Sun, Haixiang
Sun, Haixiang
中科院分区:
生物学4区
文献类型:
--
作者:
Jiang, Yue;Hu, Yali;Sun, Haixiang

文献摘要

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催乳素 (PRL) 由多种垂体外组织合成和释放,包括蜕膜基质细胞。尽管蜕膜 PRL 在妊娠期间发挥着重要作用,但人们对蜕膜 PRL 表达的正确调节所涉及的因素知之甚少。在这里,我们提供的证据表明,转录因子 Nur77 在人子宫内膜基质细胞 (hESC) 的蜕膜催乳素表达中发挥着积极作用。在 8-Br-cAMP 和醋酸甲羟孕酮 (MPA) 刺激蜕膜化后,hESC 中的 Nur77 mRNA 表达显着增加。腺病毒介导的 Nur77 在 hESC 中的过表达显着增加了 PRL mRNA 表达,并以浓度依赖性方式增强了蜕膜 PRL 启动子 (dPRL/-332Luc) 活性。此外,hESC 中 Nur77 的敲低显着降低了蜕膜 PRL 启动子的激活,并显着减弱了 8-Br-cAMP 和 MPA 诱导的 PRL mRNA 表达和 PRL 分泌 (P < 0.01)。这些结果表明,Nur77 是一种新型转录因子,对人子宫内膜基质细胞催乳素基因表达的调节有显着贡献。 (C) 2010 Elsevier Inc. 保留所有权利。
Prolactin (PRL) is synthesized and released by several extrapituitary tissues, including decidualized stromal cells. Despite the important role of decidual PRL during pregnancy, little is understood about the factors involved in the proper regulation of decidual PRL expression. Here we present evidence that the transcription factor Nur77 plays an active role in decidual prolactin expression in human endometrial stromal cells (hESCs). Nur77 mRNA expression in hESCs was significantly increased after decidualization stimulated by 8-Br-cAMP and medroxyprogesterone acetate (MPA). Adenovirus-mediated overexpression of Nur77 in hESCs markedly increased PRL mRNA expression and enhanced decidual PRL promoter (dPRL/-332Luc) activity in a concentration-dependent manner. Furthermore, knockdown of Nur77 in hESCs significantly decreased decidual PRL promoter activation and substantially attenuated PRL mRNA expression and PRL secretion (P < 0.01) induced by 8-Br-cAMP and MPA. These results demonstrate that Nur77 is a novel transcription factor that contributes significantly to the regulation of prolactin gene expression in human endometrial stromal cells. (C) 2010 Elsevier Inc. All rights reserved.