Lanoix Dave, Ouellette Rodney, Vaillancourt Cathy
Department of Chemistry and Biochemistry, Université de Moncton, Moncton, New Brunswick, Canada.
Hum Reprod. 2006 Aug;21(8):1981-9. doi: 10.1093/humrep/del120. Epub 2006 Apr 21.
Melatonin crosses the placenta and enters the fetal circulation. Moreover, experimental data suggest a possible influence of melatonin on placental function and fetal development in humans. To date, the expression and role of melatonin receptors in human placenta choriocarcinoma cell lines and in human term placental tissues remain to be elucidated.
Results from RT-PCR, western blotting and confocal microscopy demonstrated that the MT1, MT2 and RORalpha1 melatonin receptors are expressed in the human term placental tissues and in choriocarcinoma cell lines JEG-3 and BeWo. Furthermore, enzyme-linked immunosorbent assay showed that 6-chloromelatonin (a melatonin agonist) inhibits, in a dose-dependent manner, forskolin-stimulated hCG-beta secretion in JEG-3 (P < 0.001) and BeWo (P < 0.05) cells but had no effect on basal human chorionic gonadotrophin (hCG-beta) levels. This effect of 6-chloromelatonin on forskolin-stimulated HCG-beta secretion was abolished by pertussis toxin (PTX), suggesting that melatonin regulates hCG-beta production by an action involving an inhibitory Gi/o protein. In PTX-treated BeWo cells, 6-chloromelatonin stimulated basal hCG-beta secretion (P < 0.001).
These results demonstrate, for the first time, the expression of melatonin receptors in human term placental tissues and in choriocarcinoma cells and suggest a possible paracrine/autocrine function for melatonin in human placenta.
褪黑素可穿过胎盘并进入胎儿循环。此外,实验数据表明褪黑素可能对人类胎盘功能和胎儿发育有影响。迄今为止,褪黑素受体在人胎盘绒毛膜癌细胞系和足月胎盘组织中的表达及作用仍有待阐明。
逆转录聚合酶链反应(RT-PCR)、蛋白质印迹法和共聚焦显微镜检查结果表明,MT1、MT2和RORα1褪黑素受体在足月胎盘组织以及绒毛膜癌细胞系JEG-3和BeWo中均有表达。此外,酶联免疫吸附测定显示,6-氯褪黑素(一种褪黑素激动剂)以剂量依赖的方式抑制JEG-3细胞(P < 0.001)和BeWo细胞(P < 0.05)中福斯高林刺激的人绒毛膜促性腺激素β(hCG-β)分泌,但对基础人绒毛膜促性腺激素(hCG-β)水平无影响。百日咳毒素(PTX)消除了6-氯褪黑素对福斯高林刺激的hCG-β分泌的这种作用,表明褪黑素通过涉及抑制性Gi/o蛋白的作用来调节hCG-β的产生。在经PTX处理的BeWo细胞中,6-氯褪黑素刺激基础hCG-β分泌(P < 0.001)。
这些结果首次证明了褪黑素受体在足月胎盘组织和绒毛膜癌细胞中的表达,并提示褪黑素在人胎盘中可能具有旁分泌/自分泌功能。