| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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
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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
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