基于Ras-ERK信号靶点探讨迟发性性腺功能减退的发生机制

Ras-ERK1/2 was involved in the regulation of late onset hypogonadism

目的：基于Ras-ERK信号通路，以ERK1/2为检测靶点，利用线粒体呼吸链相关基因Cox7a2在TM3睾丸Leydig细胞表达为模型，探讨LOH发生及信号调控机制。方法通过分子克隆构建载体，利用细胞培养及转染模型，通过荧光显微镜观察融合蛋白及其突变体的表达及定位，探讨融合蛋白之间的共定位特点及相互作用。利用Western blot方法检测ERK1/2磷酸化水平。结果在TM3 Leydig细胞中，Cox7a2抑制ERK1/2磷酸化水平。Cox7a2与Ras信号蛋白可能存在相互作用。结论 Ras-ERK信号通路参与LOH发生机制的调控，Cox7a2参与睾丸间质细胞睾酮合成的调控，至少与抑制ERK1/2磷酸化水平有关，具体机制值得深入研究。

Objective To investigate the molecular mechanism of LOH by analyzing the effect of Cox7a2 on the LH-induced testosterone production through the interconnection of Cox7a2 and Ras-ERK. Methods Cox7a2 and its site-mutant vectors were cloned by RT-PCR and sequence analysis. The relevant fluorescent protein vectors were constructed and transfected into TM3 cells and were observed by fluorescent microscope. The phosphorylation of ERK1/2 （extra cellular signal regulated kinase1/2） was detected in TM3 Leydig cells by Western blott. Results Cox7a2 inhibited ERK1/2 phosphorylation in TM3 mouse Leydig cells stimulated with LH. Ras protein affected the sub-cellular location of Cox7a2. Conclusion Ras-ERK signaling pathway may be involved in the development of LOH. Cox7a2 mediates testosterone productionby inactivation of ERK1/2, which need to be further investigated.