Study on effects of endocrine disrupter on cleft lip and/or palate.

作为一种环境因素，我们利用双酚a （BPA）研究了尿激酶型纤溶酶原激活物（u-PA）作为血管发育标志物的抑制作用。BPA对u-PA的产生没有抑制作用。另一方面，叶酸的代谢影响唇裂和/或腭裂的原因。为了阐明这一点，我们测定了几个与叶酸代谢相关的基因表达。提示BPA可能通过视黄酸受体部分调节骨代谢相关基因的转录，从而抑制唇腭裂的发生。此外，通过综合筛选天然维甲酸受体或雌激素受体激动剂来预防唇腭裂的发展，我们从汉布药物中使用的粗药物中分离出一些RAR激动剂。

As an environmental factor, the inhibition of the production of urokinase-type plasminogen activator (u-PA) as a marker of vascular development was studied using bisphenol A (BPA). The u-PA production was not inhibited by BPA. On the other hand, the metabolism of folate affects the cause of cleft lip and/or palate. To clarify this point, several gene expressions related with folate metabolism were determined.It is suggested that BPA is likely to partly modulate the transcription of the genes involved in bone metabolism through retinoic acid receptor, resulting in the suppression of the development of a cleft lip and/or palate. Further, through the comprehensive screening of natural retinoic acid receptor or estrogen receptor agonists to prevent the development of a cleft lip and/or palate, we isolated a few RAR agonists from crude drugs used in Kampo medicines.