Molecular analysis of human parturition using oxytocin receptor

我们对人催产素受体的分子内分泌学进行了研究，主要结果如下：(1)利用COS-7细胞和非洲爪哇卵母细胞构建了人催产素受体的瞬时表达系统。用这些细胞对催产素相关多肽的结合和电生理特性进行了研究。该系统适用于新型催产素受体拮抗剂的开发。(2)建立了抗OTR的单抗。结合原位杂交结果，我们明确了OTR在分娩前后的时间和空间表达，提示临产后绒毛-蜕膜中有OTR的诱导。(3)成功地从妊娠期刮取的宫颈细胞中检测到OTRmRNA。这项技术将用于早产的预测。(4)克隆了人OTR基因。该基因定位于3号染色体(3p26.2)上，为单拷贝基因。将OTR基因5‘端非翻译区序列与已知的转录因子共同序列进行比对，发现了与核因子-IL-6、APRE、AP-1、AP-2、GAT-1、Myb等的结合位点，也发现了雌激素反应元件的一半结合位点。这些结果将引导人们对分娩和早产的分子机制有新的认识。

We investigated molecular endocrinology of human oxytocin receptor (OTR) and we obtained the results as follows :(1) We constructed the transient expression system of OTR using COS-7 cells and Xenopus laevis oocytes. With these cells, binding and electrophysiological charactor of OTR to several oxytocin related peptides were examined. This system can be adapted to the development of novel oxytocinergic antagonists.(2) We establishied anti OTR monoclonal antibodies. Combined with the result of in situ hybridization, we clarified temporal and spatial expression of OTR around parturition and indicated the induction of OTR in chorion-decidua after the onset of labor.(3) We succeeded the detection of OTR mRNA from scraped endocervical cells during pregnancy in a non-invasive manner. This techneque will be used for the prediction of preterm labor.(4) We cloned the human OTR gene. It locates on chromosome 3 (3p26.2) as a single copy gene. Compared the seguence of 5'-untranslated region of OTR gene with known consensus sequences of transcription factors, we found binding sites for NF-IL6, APRE,AP-1, AP-2, GAT-1, Myb, etc. We also found half sites for estrogen responsive element. These results will lead the novel understanding of the molecular mechanism of labor and preterm labor.