Endocrine disrupting effect of di-(2-ethylhexyl) phthalate on female rats and proteome analyses of their pituitaries
Endocrine disrupting effect of di-(2-ethylhexyl) phthalate on female rats and proteome analyses of their pituitaries
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DOI：
10.1002/pmic.200401344
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
Sakamoto, Y
中科院分区：
文献类型：
--
作者：
Hirosawa, N;Yano, K;Sakamoto, Y
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，可能对人类生殖健康产生不利影响。我们研究了DEHP对雌性大鼠的长期暴露影响，并观察到对发情周期的强烈影响，产生连续的发情阶段。我们发现，实验组大鼠血清雌二醇、卵泡刺激素（FSH）、垂体FSH和黄体生成素水平均显著降低。为了研究内分泌干扰效应，我们对它们的垂体进行了基于蛋白质组的分析，发现两种蛋白质的水平显著降低。经斑点差异统计分析，它们分别为含缬草苷肽/p97 （VCP/p97）和UMP-CMP激酶，平均蛋白斑点强度分别为0.13和0.21。此外，还有14种蛋白质的水平发生了显著变化，13种蛋白质的平均斑点强度在0.26 ~ 0.50之间，1种蛋白质的平均斑点强度在2.74之间。7蛋白水平的降低似乎与细胞内蛋白转运途径有关，似乎表明促性腺激素释放能力的减慢。垂体促性腺激素释放的减少似乎导致血清雌二醇水平的降低和发情周期中持续的发情期。
Di-(2-ethylhexyl)phthalate (DEHP) is a plasticizer and a ubiquitous environmental contaminant that may have adverse effects on human reproductive health. We examined the long-term exposure effects of DEHP on female rats and observed a strong effect on estrous cyclicity that produced a continuous diestrous stage. We found that the serum estradiol, follicle-stimulating hormone (FSH), pituitary FSH and luteinizing hormone levels were significantly reduced in the treated rats. To examine on the endocrine disrupting effects, we performed proteome-based analyses of their pituitaries, and found two proteins with remarkably reduced their levels. They were identified as the valosin-containing peptide/p97 (VCP/p97) and UMP-CMP kinase and their average protein spot intensities on statistical analysis of the spots differences of the treated/control rats were 0.13 and 0.21, respectively. Furthermore, there were 14 other proteins that had significantly changed levels, and their average protein spot intensities were in a range of 0.26 to 0.50 in 13 proteins and 2.74 in one. The reduction of in level of 7 proteins seems to be related to the intracellular protein transporting pathway, and it appears to suggest a slow down of gonadotrophin-releasing capability. Reduction of gonadotrophin release in the pituitary seems to lead to a decrease of serum estradiol level and continuous diestrous stage in estrous cyclicity.