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膜結合型ペプチダーゼ阻害剤ベスタチンの卵胞発育促進作用の解析

膜结合肽酶抑制剂贝斯汀促卵泡生长作用分析

基本信息

批准号：
13671709
负责人：
YOSHIOKA Shinya
金额：
$ 2.24万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671709/
关键词：
infertility membrane-bound peptidase follicle ovary granulose cell theca cell bioactive peptide

项目摘要

Ovulation induction is a very important therapy for most infertile women. However, in some cases, gonadotropin therapy, which is widely used as the main therapy for ovulation induction in the world, cannot make the follicles grow in the ovary. In such cases, there are no effective tfierapies so far. Therefore, a new assisted therapy for ovulation induction that locally regulates the effects of gonadotropin is necessary to solve this problem. Although many studies clarified that various peptides such as cytokines and growth factors play important roles as local regulators in folliculogenesis, a new ovulation induction therapy using these peptides has not been established yet. We reported several membrane-bound peptidases are expressed in human follicle and these peptidases are suggested to locally control the ovarian cell functions by regulating the concentration of bioactive peptides. In addition, the study using inhibitors of these peptidases implied that they regulate the effects of gonadotropin locally. In this study, we examined the effects of bestatin, inhibitor of aminopeptidase, in folliculogenesis for the purpose of clinical use. The culture of human or porcine follicles, granulose cells or theca cells showed that bestatin affected folliculogenesis and steroidogenesis of these cells under gonadotropin stimulation. Although the substrates of these membrane-bound peptidase in ovary has not been found, the way of bestatin's effects suggested that bestatin has possibility to be utilized as therapy for polycystic ovary that often causes the ovulation disturbance

诱导排卵是大多数不孕妇女的一种非常重要的治疗方法。但是，在某些情况下，目前世界上广泛使用的促性腺激素疗法作为促排卵的主要疗法，不能使卵泡在卵巢中生长。在这种情况下，迄今没有有效的补救措施。因此，一种新的辅助排卵诱导治疗，局部调节促性腺激素的作用是必要的，以解决这个问题。虽然许多研究阐明了各种肽如细胞因子和生长因子在卵泡发生中作为局部调节剂发挥重要作用，但使用这些肽的新的促排卵疗法尚未建立。我们报道了几种膜结合肽酶在人卵泡中的表达，这些肽酶可能通过调节生物活性肽的浓度来局部控制卵巢细胞的功能。此外，使用这些肽酶抑制剂的研究表明，它们局部调节促性腺激素的作用。在这项研究中，我们研究了氨基肽酶抑制剂bestatin在卵泡发生中的作用，以供临床使用。人或猪卵泡、颗粒细胞或卵泡膜细胞的培养表明，在促性腺激素刺激下，bestatin影响这些细胞的卵泡发生和类固醇合成。虽然这些膜结合肽酶在卵巢中的作用底物尚未发现，但bestatin的作用途径提示bestatin有可能用于治疗常引起排卵障碍的多囊卵巢