Chou Chun-Shan, Zhu Hua, Shalev Eliezer, 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. 2002 Dec;87(12):5594-603. doi: 10.1210/jc.2002-020883.
The regulated expression of the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1) is believed to modulate the invasive capacity of human trophoblastic cells in vitro and in vivo. To date, the factors capable of regulating the expression of uPA and PAI-1 in these cells remain poorly characterized. In these studies, we have examined the ability of the classical mammalian GnRH I and the second form of GnRH (GnRH II) to regulate uPA and PAI-1 mRNA and protein expression levels in primary cultures of human extravillous cytotrophoblasts using quantitative competitive PCR and ELISA, respectively. Both GnRH I and II increased uPA and concomitantly decreased PAI-1 mRNA and protein expression levels in our extravillous cytotrophoblast cultures in a dose- and time-dependent manner. Cetrorelix, a peptide GnRH antagonist specific for the GnRH I receptor, was capable of inhibiting the regulatory effects of GnRH I, but not GnRH II on uPA and PAI-1 expression levels in primary cell cultures. Taken together, these observations suggest that GnRH I and GnRH II may facilitate trophoblast invasion by increasing the ratio of uPA/PAI-1 expression via interactions with two distinct GnRH receptors.
尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂（PAI - 1）的调控表达被认为在体外和体内调节人滋养层细胞的侵袭能力。迄今为止，能够调节这些细胞中uPA和PAI - 1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ELISA检测了经典的哺乳动物促性腺激素释放激素I（GnRH I）和第二种促性腺激素释放激素（GnRH II）调节人绒毛外细胞滋养层原代培养物中uPA和PAI - 1 mRNA及蛋白表达水平的能力。在我们的绒毛外细胞滋养层培养物中，GnRH I和II均以剂量和时间依赖性方式增加uPA，并同时降低PAI - 1 mRNA和蛋白表达水平。西曲瑞克是一种对GnRH I受体具有特异性的肽类GnRH拮抗剂，它能够抑制GnRH I对原代细胞培养物中uPA和PAI - 1表达水平的调节作用，但不能抑制GnRH II的调节作用。综上所述，这些观察结果表明，GnRH I和GnRH II可能通过与两种不同的GnRH受体相互作用，增加uPA/PAI - 1表达的比值，从而促进滋养层细胞的侵袭。
