促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)是牛殖过程中起重要调节作用的激素.近年来的研究发现,Ⅰ型CmRH(GnRHⅠ)和Ⅱ型GnRH(GnRHⅡ)在胎盘和胎盘来源的滋养层细胞中发挥生理功能.利用人滋养层细胞模型人绒毛膜上皮癌细胞系(JEG-3)细胞,探讨GnRHⅠ和GnRHⅡ对人滋养层细胞侵润的调节作用.荧光实时定量PCR证实,GnRHI和GnRHⅡ可调节JEG-3细胞中经典GnRH受体(GnRHRⅠ)的表达.RNA干扰实验显示,特异性针对GnRHRⅠ的siRNA可显著阻断GnRHⅠ对JEG-3细胞的促侵润作用,但不能影响GnRHⅡ的促细胞侵润功能,提示GnRHⅡ可能通过经典GnRH受体以外的其他受体介导,以发挥促进滋养层细胞侵润的功能.对信号通路的进一步研究表明,GnRⅠ-Ⅱ和GnRHⅡ通过ERK和JNK激酶级联促进基质金属蛋白酶-2(MMP-2)的表达,以调节细胞的侵润.
Mammalian gonadotropin-releasing hormone (termed GnRH Ⅰ ) is a decapeptide that plays key role in the process of reproduction. In addition to its well-known endocrine function, it has become evident that GnRH Ⅰ and the second GnRH subtype (termed GnRH Ⅱ ) are potentially important autocrine and/or paracrine regulators in placental trophoblast cells. The effects of GnRHⅠ and GnRH Ⅱ on trophoblastic cell invasion were investigated in human choriocarcinoma cell line (JEG-3) by the methods of invasion assay, RNA interference, Western blot and Real-time PCR. The data revealed that exogenous native peptide of these two forms of GnRH significantly induced the expression of type Ⅰ GnRH receptor (GnRHR Ⅰ ) in JEG-3 cells. The specific siRNA for GnRHR Ⅰ was capable of blocking the invasion-promoting effect of GnRH Ⅰ, but did not influence the effect of GnRH Ⅱ. The data suggested that the two hormones may be elicited by distinct receptors. Interference of the activities of ERK and JNK was capable of attenuating GnRH Ⅰ and Ⅱ -induced MMP-2 expression and tropboblast invasion, indicating that activation of ERK and JNK are required in both GnRH Ⅰ and GnRH Ⅱ -mediated MMP-2 production and invasion-promoting effect in human trophoblastic cells.