Molecular analysis of human parturition using oxytocin receptor

使用催产素受体对人类分娩进行分子分析

• 批准号: 05454449
• 负责人: KIMURA Tadashi
• 金额: $ 4.29万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454449/
• 关键词: oxytocin; oxytocin receptor; transient expression; monoclonal antibodies; gene; transcriptional regulation; 一過性発現系; オキシトシン受容体遺伝子; 5′上流領域; in situ hybridization; 抗ヒトオキシトシン抗体

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.

本研究对人催产素受体（OTR）的分子内分泌学进行了研究，主要结果如下：（1）利用COS-7细胞和非洲爪蟾卵母细胞构建了OTR的瞬时表达系统。利用这些细胞，研究了OTR与几种催产素相关肽的结合和电生理特性。该系统可适用于开发新的催产素能拮抗剂。(2)建立了抗OTR单克隆抗体。结合原位杂交结果，阐明了OTR在分娩前后的时空表达，并提示了临产后OTR在绒毛-蜕膜中的诱导表达。(3)我们成功地检测OTR mRNA从刮子宫颈内膜细胞在怀孕期间在一个非侵入性的方式。这项技术将用于早产的预测。(4)我们克隆了人类OTR基因。该基因定位于3号染色体（3p26.2），为单拷贝基因。将OTR基因5 '端非翻译区序列与已知转录因子的保守序列进行比较，发现了NF-IL 6、APRE、AP-1、AP-2、GAT-1、Myb等转录因子的结合位点，并发现了雌激素反应元件的半位点。这些研究结果将有助于对分娩和早产的分子机制有新的认识。

项目成果

Masahiko Takemura et al.: "Expression and localization of human oxytocin receptor mRNA and its protein in chrion and decidua during parturition." J.Clin. Invest.93. 2319-2323 (1994)

Masahiko Takemura 等人：“分娩过程中人催产素受体 mRNA 及其蛋白质在绒毛膜和蜕膜中的表达和定位。”

Tadashi Kimura et al.: "Molecular cloning of a human oxytocin receptor." Regulatory Peptides. 45. 73-77 (1993)

Tadashi Kimura 等人：“人类催产素受体的分子克隆。”

木村 正他: "Annual Review内分泌・代謝1994" 岡 博他, 287 (1994)

Tadashi Kimura 等人：“Annual Review Endocrinology and Metabolism 1994” Hiroshi Oka 等人，287 (1994)

Masahiko Takemura et al.: "Expression and localization of human oxytocin receptor mRNA and its protein in chorion and decidua during parturitio" J.Clin.Invest.93. 2319-2323 (1994)

Masahiko Takemura 等人：“分娩过程中人催产素受体 mRNA 及其蛋白质在绒毛膜和蜕膜中的表达和定位”J.Clin.Invest.93。

Tadashi Kimura et al: "Molecular cloning of a human oxytocin receptor" Regulatory Peptides. 45. 73-77 (1993)

Tadashi Kimura 等人：“人催产素受体的分子克隆”调节肽。