Endocrine disrupting effect of Di - (2 - ethylhexyl) phthalate on rats and proteome analysis of their pituitary and hypothalamus

邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种增塑剂，是一种普遍存在的环境污染物，对人类生殖健康有不利影响。此外，目前还没有发现DEHP与性激素受体结合的报道。因此，影响活体内分泌功能的作用方式尚不清楚。在本实验中，我们研究了DEHP对大鼠胚胎和幼鼠的影响。本工作利用孕鼠和哺乳鼠分别研究DEHP对胎儿和婴儿的影响，并对这些幼鼠的内分泌器官进行蛋白质组学分析。对照组仅给予芝麻油灌胃。妊娠组自妊娠第2天起给予DEHP 15次，剂量为0.5g/kg/d。哺乳组从…第2天开始，按相同剂量连续给药17次。更多的是在送货之后。各给药期结束后，将仔鼠与母鼠分开饲养4个月，取出内分泌器官，治疗组与对照组体重无明显差异，但孕期及哺乳期仔鼠脑垂体重量显著增加(p&gt；0.05)。因此，间接摄入DEHP似乎对幼年大鼠的脑垂体有影响，因此，用双向电泳法对三组大鼠脑垂体进行了蛋白质差异分析。找到了四个感兴趣的蛋白质点，并对这些蛋白质进行了蛋白质组学分析。结果，通过MSCOT(http://www.matrixscience.com).)数据库检索，这些蛋白质被鉴定为生长激素受体、腺嘌呤磷酸核糖基转移酶、蛋白酶激活物复合体亚基1和禁忌素这些蛋白质似乎反映了DEHP对活体的影响，对于阐明DEHP的内分泌干扰作用机制具有重要意义。较少

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer and is a ubiquitous environmental contaminant which may have adverse effects on human reproductive health. Additionally, no binding ability of DEHP to sex hormone receptors already reported. Therefore, a mode of action affecting an endocrine function of a living body is not clarified.In this examination, we investigated about the affection of DEHP to fetus and infant of rat. Pregnant and lactation rats are used in this working the effect of DEHP to the fetus and infant, respectively and carried out proteome-based analyses of the endocrine organs of these child rats.Control group, pregnant group and lactation group of F344 rats are prepared. In control group, only administrations of sesame oil were carried out. In pregnant group, 15 times of administrations of DEHP were performed with a dose of the 0.5g/kg/day from after 2 days of pregnancy. In lactation group, 17 times of administrations are done with the same dosage from 2^<nd> day a … More fter delivery. After the each administration period, child rats were separated form mother rats and were bred for 4 month in no administration, and then endocrine organs of them were eviscerated.No significant body weights were found between the treated or control group but pituitaries weight were significantly increased in child rats of pregnant and lactation group (p > 0.05). Thus the indirect intake of DEHP seemed to be affective on pituitary of child rats, therefore, protein difference analyses with two-dimensional electrophoresis were performed on the pituitary in the three groups. Four interest protein spots were found and proteome based analyses for these proteins were performed. As a result, these proteins were identified to be somatotropin receptor, adenine phosphoribosyltransferase, proteaseme activator complex subunit1 and prohibin through the study of the database search with MSCOT (http://www.matrixscience.com). These proteins seems to be reflecting the effect of DEHP to living body and to be important for elucidating the endocrine disrupting effect mechanism of DEHP. Less