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首页> 外文期刊>Environmental toxicology and chemistry >MODULATION OF ESTROGEN SYNTHESIS THROUGH ACTIVATION OF PROTEIN KINASE A IN H295R CELLS BY EXTRACTS OF ESTUARY SEDIMENTS
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MODULATION OF ESTROGEN SYNTHESIS THROUGH ACTIVATION OF PROTEIN KINASE A IN H295R CELLS BY EXTRACTS OF ESTUARY SEDIMENTS

机译：沉积物提取物通过活化H295R细胞中的蛋白激酶A调节雌激素合成

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摘要

Sediments from two estuaries within Liaodong Bay, China, were examined for the effects on steroidogenesis using H295R human adrenocortical carcinoma cells. Total extracts (TE) isolated from sediments by Soxhlet extraction were separated into three fractions (F1, F2, and F3) using Florisil columns. After exposing H295R cells to each TE and fractions, the expressions of six steroidogenic genes (cytochrome P450 cholesterol side-chain cleavage [CYP11A], 3β-hydroxysteroid dehydrogenase type 1 [3β-HSD1], 3β-hydroxysteroid dehydrogenase type 2 [3β-HSD2], cytochrome P450 17-hydroxylase/17-20 lyase [CYP17], cytochrome P450 aromatase [CYP19], 17β-hydroxysteroid dehydrogenase [17β-HSD]), and the production of six steroid hormones (progesterone [PGT], 17-hydroxyprogesterone [17-HPT], testosterone [TTR], androstenedione [ADD], estrone [E1], and 17β-estradiol [17β-E2]) were measured. The gene expressions of CYP11A, CYP17, 3β-HSD2, and CYP19, and hormone productions of PGT, 17-HPT, TTR, ADD, E1, and 17β-E2 were significantly increased after exposure to F3 extracts from the Daliao River. In particular, greater concentrations of El (up to 48-fold) and 17β-E2 (up to 20-fold), as well as up-regulation of CYP19 gene expression (up to tenfold), were caused by exposure to the F3 fraction from the Daliao River, but not from the Daling River. Insight into the mechanism of action was obtained by use of principal component analysis (PCA), the results of which were consistent with unidentified constituents in F3 from the Daliao River activating the protein kinase A (PKA) pathway. This hypothesis was confirmed by reversal of the effects caused by F3 through a co-exposure of a PKA inhibitor (H89) and F3 extract. The H89 down-regulated CYP19 messenger RNA (mRNA) expression with concomitant lesser production of El and 17β-E2 in the co-exposure group, indicating unidentified constituents that could modulate estrogen synthesis, primarily through a mechanism of PKA activation.
机译：使用H295R人肾上腺皮质癌细胞研究了中国辽东湾两个河口的沉积物对类固醇生成的影响。使用弗洛里西尔色谱柱通过索氏提取法从沉积物中分离出的总提取物（TE）分为三部分（F1，F2和F3）。将H295R细胞暴露于每个TE和组分后，表达六个类固醇生成基因（细胞色素P450胆固醇侧链裂解[CYP11A]，3β-羟基类固醇脱氢酶1型[3β-HSD1]，3β-羟基类固醇脱氢酶2型[3β-HSD2] ]，细胞色素P450 17-羟化酶/ 17-20裂解酶[CYP17]，细胞色素P450芳香化酶[CYP19]，17β-羟基类固醇脱氢酶[17β-HSD]）和六种类固醇激素（孕酮[PGT]，17-羟基孕酮）的产生测量了[17-HPT]，睾丸激素[TTR]，雄烯二酮[ADD]，雌酮[E1]和17β-雌二醇[17β-E2]。暴露于大辽河的F3提取物后，CYP11A，CYP17、3β-HSD2和CYP19的基因表达以及PGT，17-HPT，TTR，ADD，E1和17β-E2的激素产生显着增加。尤其是，暴露于F3组分会导致更高浓度的El（最高48倍）和17β-E2（最高20倍）以及CYP19基因表达的上调（最高10倍）来自大辽河，但不来自大凌河。通过使用主成分分析（PCA）了解了作用机理，其结果与大辽河激活蛋白激酶A（PKA）途径的F3中未确定的成分一致。通过共同暴露PKA抑制剂（H89）和F3提取物来逆转F3引起的影响，证实了这一假设。 H89下调CYP19信使RNA（mRNA）的表达，同时暴露组中El和17β-E2的产生较少，这表明主要是通过PKA激活的机制，未知的成分可以调节雌激素的合成。

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  • 来源
    《Environmental toxicology and chemistry》 |2011年第12期|p.2793-2801|共9页
  • 作者

    Chong Huang; Shimin Wu; Xiaowei Zhang; Hong Chang; Yanbin Zhao; John P. Giesy; Jianying Hu;

  • 作者单位

    MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

    MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

    State Key Laboratory of Pollution Control and Resource Reuse and School of the Environment, Nanjing University, Nanjing, China;

    MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

    MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

    Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada,Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan, USA,Zoology Department, King Saud University, Riyadh, Saudi Arabia;

    MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    H295R assay; steroidogenesis; estrogen synthesis; toxicity identification;

    机译：H295R分析;类固醇生成雌激素合成毒性鉴定;

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