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Vitamin A modulates the effect of estrogen on cell differentiation

维生素 A 调节雌激素对细胞分化的影响

基本信息

批准号：
13640662
负责人：
MORI Takao
金额：
$ 2.18万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

In this study, we introduced estrogen and bisphenol as an endocrine disruptor and vitamin A as an inhibitor of the effect of such endocrine disrupters on the developing reproductive system in female and male mice. The results also suggested that, to a certain extent, the replenishment of vitamin A-rich food is important for relieving the effect of endocrine disruption in babies, caused by exogenous estrogenic substances, since the effect of such substances on the developing reproductive tracts should exert via vitamin A deficiency. On the other hand, unusual mRNA expression of a cellular retinol binding protein 2, which regulates the metabolism of vitamin A, was found in the reproductive tracts after neonatal exposure to estrogen. Therefore, it could be proposed that the neonatal effects of both estrogen and bisphenol A on the vaginal differentiation and spermatogenesis are exerts through the suppression of vitamin A action. Although the interaction of vitamin A with estrogenic substances during a critical period was not clarified, a possible explanation is conceivable : 1) at first, neonatal treatment with estrogenic substances leads to the disruption of vitamin A metabolism and/or transportation in the reproductive tracts ; 2) the direction of normal differentiation of the reproductive tracts is changed by a lack of appropriate vitamin A action ; 3) the reproductive tracts, of which the direction of normal differentiation is changed, receive the continuing estrogenic stimulation as a proliferation signal ; and 4) the reproductive tracts differentiate to an abnormal direction.

在这项研究中，我们介绍了雌激素和双酚作为内分泌干扰物和维生素A作为这种内分泌干扰物对雌性和雄性小鼠生殖系统发育的影响的抑制剂。结果还表明，在一定程度上，补充富含维生素A的食物对于缓解外源性雌激素物质引起的婴儿内分泌干扰的影响是重要的，因为这些物质对发育中的生殖道的影响应通过维生素A缺乏来发挥。另一方面，在新生儿暴露于雌激素后的生殖道中发现了调节维生素A代谢的细胞视黄醇结合蛋白2的不寻常的mRNA表达。因此，可以提出，雌激素和双酚A对阴道分化和精子发生的新生儿效应是通过抑制维生素A的作用来发挥的。虽然维生素A与雌激素物质在关键时期的相互作用尚未阐明，但可以设想一种可能的解释：1）最初，用雌激素物质治疗新生儿导致生殖道维生素A代谢和/或运输的中断：2）由于缺乏适当的维生素A作用，生殖道的正常分化方向改变; 3）正常分化方向改变的生殖道接受持续的雌激素刺激作为增殖信号; 4）生殖道向异常方向分化。