Analysis of Lysophosphatidic acid Receptors in the Uterine Endometrium During the Proliferative and Secretory Phases and in Endometrial Hyperplasic and Cancer Tissues in Human

초록

Lysophosphatidic acid (LPA) is a simple phospholipid composed of a glycerol or sphingoid backbone with a fatty acid of varied length and saturation. LPA induces many growth factor-like effects including cell proliferation, migration, and differentiation in various tissues. LPA actions are mediated through specific G-protein coupled receptors, and the presence of six isoforms of LPA receptors, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5 and LPAR6, have been reported so far in human. Expression of LPARs has been shown in many human and animal tissues, but expression of LPARs in the human endometrium during the menstrual cycle has not been studied. Thus, this study determined expression of LPAR1 – LPAR6 in the uterine endometrium during the proliferative and secretory phases in human. Real-time RT-PCR analysis determined that all LPA receptors were present and that abundance of LPAR3 mRNA in the endometrium was higher during the proliferative phase than those during the secretory phase, while abundance of LPAR5 mRNA was higher during the secretory phase than during the menstrual cycle. Furthermore, we analyzed expression of LPAR receptors in endometrial hyperplasic and cancer tissues, and real-time RT-PCR analysis showed that abundance of LPAR2, LPAR3, LPAR5 and LPAR6 mRNAs was significantly higher in hyperplasic tissues than that in the endometrium during the proliferative phase. In endometrial cancer tissues, expression of LPAR5 and LPAR6 mRNAs was significantly increased compared with that in the endometrium during the proliferative phase. These results showed that LPA receptors were differentially expressed in the uterine endometrium during the menstrual cycle and expression of some LPA receptors increased in endometrial hyperplasic and cancer tissues. These results indicate that LPA plays a critical role in endometrial functions during the menstrual cycle and in the formation of endometrial hyperplasia and cancer. Further analysis is needed to understand cellular and molecular mechanisms of LPA actions in the uterine endometrial functions in human.