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

促排卵对大多数不孕妇女来说是非常重要的治疗方法。然而，在某些情况下，促性腺激素治疗不能使卵泡在卵巢中生长，促性腺激素治疗是世界上广泛使用的促排卵主要治疗方法。在这种情况下，迄今为止还没有有效的治疗方法。因此，需要一种局部调节促性腺激素作用的新的辅助促排卵疗法来解决这一问题。尽管许多研究表明，多种多肽如细胞因子和生长因子在卵泡发生中起着重要的局部调节作用，但尚未建立一种新的使用这些多肽的促排卵治疗方法。我们报道了几种膜结合肽酶在人卵泡中表达，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功能。此外，使用这些肽酶抑制剂的研究表明，它们可以局部调节促性腺激素的作用。在这项研究中，我们检测了百他汀，氨基肽酶抑制剂，在卵泡生成中的作用，以供临床使用。人或猪卵泡、颗粒细胞或卵泡细胞的培养表明，在促性腺激素刺激下，贝司他汀影响这些细胞的卵泡生成和类固醇生成。虽然这些膜结合肽酶在卵巢中的底物尚未被发现，但贝司他汀的作用方式提示贝司他汀有可能用于治疗多囊卵巢这种常引起排卵障碍的疾病

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