Viswanath G, Chatterjee S, Roy P
Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttaranchal, India.
Mol Cell Endocrinol. 2007 Jun 30;272(1-2):14-21. doi: 10.1016/j.mce.2007.04.006. Epub 2007 May 4.
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) play an important role in the development and maintenance of male and female gonads. Both these hormones act through the same specific receptor LH/hCG receptor (LHR). Recent studies have shown the existence of functional LHR in several non-gonadal tissues. The aim of this study was to confirm the functional existence of LHR in an endometrial adenocarcinoma cell line, Ishikawa cells, which has been used since long as an in vitro uterine endometrium model. Reverse transcriptase-polymerase chain reaction (RT-PCR) data showed the stable expression of LHR in this cell line. However, the receptor failed to activate the PKA pathway in response to hCG, which is the most conventional mode of LH/hCG action in target tissues. When tested for other pathways, hCG failed to activate them either. Nested RT-PCR confirmed the existence of full-length LHR and this was further supported by Western blot. This study demonstrated that although Ishikawa cells do possess a full-length LHR, which was confirmed by RT-PCR, nested RT-PCR, Western blot and DNA sequencing, it failed to activate the conventional LH-mediated downstream signaling. Based on these data we hypothesize that in Ishikawa cells LH/hCG does not utilize its conventional receptor. Whether it acts through some other receptor is a question, which can be answered through future research.
促黄体生成素(LH)和人绒毛膜促性腺激素(hCG)在男性和女性性腺的发育与维持中发挥着重要作用。这两种激素均通过同一特异性受体——LH/hCG受体(LHR)发挥作用。最近的研究表明,在几种非性腺组织中存在功能性LHR。本研究的目的是证实LHR在子宫内膜腺癌细胞系 Ishikawa细胞中的功能性存在,该细胞系长期以来一直被用作体外子宫内膜模型。逆转录聚合酶链反应(RT-PCR)数据显示该细胞系中LHR表达稳定。然而,该受体未能响应hCG激活PKA途径,而hCG激活PKA途径是LH/hCG在靶组织中最常见的作用方式。当检测其他途径时,hCG也未能激活它们。巢式RT-PCR证实了全长LHR的存在,蛋白质印迹法进一步支持了这一结果。本研究表明,尽管 Ishikawa细胞确实拥有全长LHR,这已通过RT-PCR、巢式RT-PCR、蛋白质印迹法和DNA测序得到证实,但它未能激活传统的LH介导的下游信号传导。基于这些数据,我们推测在Ishikawa细胞中,LH/hCG不利用其传统受体。它是否通过其他受体发挥作用是一个问题,这可以通过未来的研究来解答。