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

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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