The effect of estrogenic endocrine disrupting chemicals on perinatal period and its mechanism

雌激素性内分泌干扰物对围产期的影响及其机制

• 批准号: 11671621
• 负责人: KUDO Takafumi
• 金额: $ 2.3万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671621/
• 关键词: endocrine Disrupting Chemical; perinatal period; estrogen receptor; nuclear rceptor; transcription; coactivator; 内分泌撹乱物質; coactivator

The endocrine disrupting chemical (EDC) has been defined as an exogenous agent that interferes with the synthesis, secretion, transport, binding, action or elimination of natural hormones in the body, which are responsible for the maintenance of homeostasis, reproduction, development and/or behavior. These chemicals can alter the endocrine functions through a variety of mechanisms, steroid hormone receptor-mediated changes in protein synthesis, interfering with membrane receptor binding, steroidogenesis, or synthesis of other hormones. Major chemicals, such as phthalates, alkylphenols, bisphenol A and DDT, have been shown to disrupt the estrogenic actions mainly through the binding to estrogen or androgen receptors. Estrogen, one of these hormones, plays several important roles during gestational period. Recently, a novel ER, referred to as ER-β, was cloned and characterized from human and rat. Although the ER-βprotein has similarities to classical ER referred to as ER-α, in terms of s … More tructure and function, the tissue distribution of both ER-αand-β in the rat are not identical appears to overlap in some tissues.We demonstrated that endocrine disrupting chemicals (EDCs), stimulated ER-mediated transcription and that ER interacted with nuclear receptor coactivator proteins, SRG1, REP140, TRAP220 and SUG1 in the presence of EDCs. Both ER-α and -β in non-pregnant rats were expressed in ovary and vagina, while only ER-α was detected in uterine under our condition. In feto-placental tissues tested here, there were the expressions of both ER-a and -p in placenta and umbilical cord, while both ER-pwas expressed in lung and brain. DM rats demonstrated that the expressions of ERs were increased in maternal ovary, umbilical cord and fetal brain, while IUGR rats showed that the expression of ER-α was decreased in uterine and that of ER-β was also decreased in placenta and fetal lung. The effect of EDC on ER expression in cell lines and in vivo were also examined. Some EDC have significant effects on the protein levels of both ERs and coactivator, TRAP220.These data suggest that EDC enhanced ER-mediated transcription and affected the target gene expressions and also have some effects on the expressions of ERs and coacrtivator. Less

内分泌干扰化学物质（EDC）被定义为一种干扰体内天然激素的合成、分泌、运输、结合、作用或消除的外源性物质，这些激素负责维持体内平衡、繁殖、发育和/或行为。这些化学物质可以通过多种机制改变内分泌功能，类固醇激素受体介导的蛋白质合成改变，干扰膜受体结合，类固醇生成或其他激素的合成。主要的化学物质，如邻苯二甲酸盐、烷基酚、双酚A和滴滴涕，已被证明主要通过与雌激素或雄激素受体结合来破坏雌激素的作用。雌激素是这些激素中的一种，在妊娠期起着几个重要的作用。最近，从人类和大鼠中克隆并鉴定了一种新的ER，称为ER-β。虽然ER-β蛋白与经典的ER-α有相似之处，但在结构和功能上，ER-α和-β在大鼠体内的组织分布并不相同，在某些组织中出现重叠。我们证明了内分泌干扰物质（EDCs）刺激ER介导的转录，并且在EDCs存在的情况下，ER与核受体共激活蛋白SRG1、REP140、TRAP220和SUG1相互作用。在本实验条件下，未妊娠大鼠卵巢和阴道中均有ER-α和-β表达，而子宫中仅检测到ER-α。在胎胎盘组织中，胎盘和脐带均有ER-a和-p的表达，肺和脑均有er -p的表达。DM大鼠在母体卵巢、脐带和胎脑中ER表达升高，IUGR大鼠在子宫中ER-α表达降低，在胎盘和胎肺中ER-β表达降低。研究了EDC对ER在细胞系和体内表达的影响。一些EDC对内质网和共激活物TRAP220的蛋白水平都有显著影响。这些数据表明，EDC增强了er介导的转录，影响了靶基因的表达，并且对er和辅因子的表达也有一定的影响。少

项目成果

Y. Hiramatsu, H. Masuyama, Y. Mizutani, T. Kudo, N. Oguni, Y. Oguni: "How to Reduce the Delivery of Heavy-For-Dates Infants ; Their Backgrounds and Relationship with Gestational Diabetes."J Obstet Gynecol Res. 26. 193-198 (2000)

Y. Hiramatsu、H. Masuyama、Y. Mizutani、T. Kudo、N. Oguni、Y. Oguni：“如何减少重产儿的分娩；他们的背景及其与妊娠糖尿病的关系。”J Obstet Gynecol

Y. Mimura, M. Kishida, H. Masuyama, N. Suwaki, J. Kodama, F. Otsuka, H. Kataoka, T. Yamauchi, T. Ogura, T. Kudo, H. Makino: "Coexistence of Graves' disease and Struma Ovarii : Case Report and Literature Review."Endocrine J. 48. 255-260 (2001)

Y. Mimura、M. Kishida、H. Masuyama、N. Suwaki、J. Kodama、F. Otsuka、H. Kataoka、T. Yamauchi、T. Ogura、T. Kudo、H. Makino：“格雷夫斯病的共存

H.Masuyama, Y.Hiramatsu, T.Kudo, et al.: "Endocrine Disrupting Chemicals Phthalic Acid and Nonylphenol Activate Pregnane X Receotor-mediated Transcriotion"Molecular Endocrinology. 14. 421-428 (2000)

H.Masuyama、Y.Hiramatsu、T.Kudo 等人：“内分泌干扰化学物质邻苯二甲酸和壬基酚激活孕烷 X 受体介导的转录”分子内分泌学。

M. Ishida, Y. Hiramatsu, H. Masuyama, Y. Mizutani, T. Kudo: "Inihibition of placental omithine decarboxylase by DL-α-difluoro-methyl omithine causes fetal growth restriction in rat."Life Sciences. 70. 1395-1405 (2002)

M. Ishida、Y. Hiramatsu、H. Masuyama、Y. Mizutani、T. Kudo：“DL-α-二氟甲基鸟氨酸抑制胎盘鸟氨酸脱羧酶导致大鼠胎儿生长受限。”生命科学 70。1395- 1405 (2002)

国富 衛, 増山 寿, 水谷靖司, 平松祐司, 工藤尚文, 他: "ラット周産期におけるEstrogen receptor-α及びβの発現"日本新生児学会雑誌. 35. 411 (1999)

Mamoru Kunitomi、Hisashi Masuyama、Yasushi Mizutani、Yuji Hiramatsu、Naofumi Kudo 等：“大鼠围产期雌激素受体-α 和 β 的表达”日本新生儿学会杂志 35. 411 (1999)。