Estimation of effects of endocrine disruptor

人们一直怀疑内分泌干扰物影响性腺的性别分化。然而，由于缺乏对性腺性别分化的分子机制的了解，其影响尚不清楚。因此，在本研究中，我们主要通过在分化性腺中表达的转录因子的功能来了解其分子机制。性别是由性染色体的组成决定的，这在受精时发生。此后，性冷淡性腺根据性别分化为睾丸或卵巢。的染色体。性腺合成和分泌的性激素在机体性别分化中起着关键作用。因此，在考虑所有动物物种的性别分化时，性腺性别决定是性别分化的关键步骤，这一点已被普遍接受。因此，我们通过关注与Ad4BP/ sf - 1相互作用的分子来研究性腺分化的分子机制，这对性腺分化至关重要。通过酵母二杂交筛选，已分离出若干分子，其中部分分子。编码转录因子和其他通过细胞生长因子编码参与信号传导的因子。其中一个转录因子具有配对的同源结构域，通过对该基因被破坏小鼠的研究和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。p-连环蛋白是一种信号转导分子。功能分析表明，β-catenin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理解性腺性别分化的分子机制

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