权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Estimation of effects of endocrine disruptor

内分泌干扰物影响的估计

基本信息

批准号：
11557078
负责人：
MOROHASHI Ken-ichirou
金额：
$ 8.7万
依托单位：
Okazaki National Research Institutes
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557078/
关键词：
gonad sex determination transcription factor Ad4BP SF-1 内分泌撹乱物質 P450 Dax-1

项目摘要

It has been suspected that endocrine disruptors affect gonad sex differentiation. However, the effects has been unclear probably because lacking our understanding the molecular mechanism underlying gonad sex differentiation. Thus, in ' the present study we focused on understanding the molecular mechanism through functions of transcription factors expressed in the differentiating gonads. Sexes are determined by composition of sex chromosomes, which is occurred at fertilization. Thereafter, sexually indifferent gonads differentiate into testis or ovary according to the sex.' chromosomes. Sex hormones synthesized and secreted from the gonads are known to play pivotal roles for sex differentiation of whole body. Thus, when considering sex differentiation of all animal species, it is well accepted that the key step for sex differentiation is the gonad sex determination. Thus, we have studied the molecular mechanism underlying the gonad differentiation by focussing on molecules interacting with Ad4BP/SF-l which is essential for gonad differentiation. Through yeast two hybrid screening, a number of molecules have been isolated, some of which.encode transcription factors and other of which encode factors implicated in signal trahsduction through cell growth factors. One of the transcription factors has a paired homeo domain, and the functional significance was clearly revealed by investigating the gene disrupted mouse and by finding a human disease caused by the gene mutation. As a molcule for signal transduction, p-catenin was isolated. Functional analysis indicated that β-catenin activated Ad4BP/SF-l mediated transcription through a direct interaction. These findings help us to understand the molecular mechanisms underlying gonad sex differentiation

人们怀疑内分泌干扰物影响性腺性别分化。然而，其影响尚不清楚，可能是因为我们缺乏对性腺性别分化的分子机制的了解。因此，在本研究中，我们重点通过分化性腺中表达的转录因子的功能来了解分子机制。性别是由受精时发生的性染色体的组成决定的。此后，性冷漠的性腺根据性别分化为睾丸或卵巢。染色体。众所周知，性腺合成和分泌的性激素对于全身的性别分化起着关键作用。因此，在考虑所有动物物种的性别分化时，人们普遍认为性别分化的关键步骤是性腺性别决定。因此，我们通过关注与性腺分化所必需的Ad4BP/SF-1相互作用的分子来研究性腺分化的分子机制。通过酵母二杂种筛选，分离出许多分子，其中一些分子编码转录因子，另一些分子编码参与细胞生长因子信号传导的因子。其中一个转录因子具有配对的同源结构域，通过研究基因破坏的小鼠并发现由该基因突变引起的人类疾病，清楚地揭示了其功能意义。作为信号转导的分子，p-连环蛋白被分离出来。功能分析表明β-连环蛋白通过直接相互作用激活Ad4BP/SF-1介导的转录。这些发现有助于我们了解性腺性别分化的分子机制