Chou Chun-Shan, MacCalman Colin D, Leung Peter C K
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
J Clin Endocrinol Metab. 2003 Aug;88(8):3806-15. doi: 10.1210/jc.2002-021955.
To date, the factors capable of regulating the coordinate expression of the urokinase-type plasminogen activator (uPA) and its endogenous inhibitor, plasminogen activator inhibitor (PAI-1), at the maternal-fetal interface remain poorly characterized. In these studies we examined the ability of the classical form of gonadotropin-releasing hormone (GnRH) I and the second, mammalian form of this hormone, GnRH II, to regulate uPA and PAI-1 mRNA and protein expression levels in cultures of stromal cells isolated from first trimester decidual tissues using quantitative competitive-PCR and ELISA, respectively. GnRH I and GnRH II increased uPA mRNA and protein expression levels in these primary cell cultures in a dose- and time-dependent manner. In contrast, GnRH I increased, whereas GnRH II decreased PAI-1 mRNA and protein expression levels in these cells. Cetrorelix, a GnRH receptor antagonist, inhibited the regulatory effects of GnRH I, but not GnRH II, on uPA and PAI-1 expression levels in these decidual stromal cell cultures. Taken together, these observations suggest that GnRH I and GnRH II differentially regulate the balance between uPA and PAI-1 expression levels in the human decidua, possibly via distinct receptor-mediated signaling pathways.
迄今为止，在母胎界面能够调节尿激酶型纤溶酶原激活物（uPA）及其内源性抑制剂纤溶酶原激活物抑制剂（PAI-1）协同表达的因素仍未得到充分表征。在这些研究中，我们分别使用定量竞争PCR和酶联免疫吸附测定法，检测了促性腺激素释放激素（GnRH）经典形式I以及该激素的第二种哺乳动物形式GnRH II调节从孕早期蜕膜组织分离的基质细胞培养物中uPA和PAI-1 mRNA及蛋白表达水平的能力。GnRH I和GnRH II在这些原代细胞培养物中以剂量和时间依赖性方式增加uPA mRNA和蛋白表达水平。相反，GnRH I增加而GnRH II降低这些细胞中PAI-1 mRNA和蛋白表达水平。GnRH受体拮抗剂西曲瑞克抑制了GnRH I对这些蜕膜基质细胞培养物中uPA和PAI-1表达水平的调节作用，但对GnRH II无此作用。综上所述，这些观察结果表明，GnRH I和GnRH II可能通过不同的受体介导信号通路，差异性地调节人蜕膜中uPA和PAI-1表达水平之间的平衡。
