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首页> 外文期刊>Comparative biochemistry and physiology, Part B. Biochemistry & molecular biology >Comparison of steroidogenic gene expression in mummichog (Fundulus heteroclitus) testis tissue following exposure to aromatizable or non-aromatizable androgens
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Comparison of steroidogenic gene expression in mummichog (Fundulus heteroclitus) testis tissue following exposure to aromatizable or non-aromatizable androgens

机译:在暴露于芳茂或非芳族化雄激素后,术语术语(基质脓性脓性血晶碱)睾丸组织的甾体基因表达的比较

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摘要

Androgens are a recognized class of endocrine disrupting compounds with the ability to impact reproductive status in aquatic organisms. The current study utilized in vitro exposure of mummichog (Fundulus heteroclitus) testis tissue to either the aromatizable androgen 17 alpha-methyltestosterone (MT) or the non-aromatizable androgen 5 alpha-dihydrotestosterone (DHT) over the course of 24 h to determine if there were differential effects on steroidogenic gene expression. Testis tissue was exposed to androgen concentrations of 10(-12) M, 10(-9) M and 10(-6) M for 6, 12, 18 or 24 h, after which a suite of steroidogenic genes, including steroidogenic acute regulatory protein, 3 beta-hydroxysteroid dehydrogenase (3 beta hsd) and cytochrome P450 17A1 (cyp17a1), were quantified using real-time polymerase chain reaction. Both androgens affected steroidogenic gene expression, with most alterations occurring at the 24-hour time point. The gene with the highest fold-change, and shortest interval to expression alteration, was 3 beta hsd for both androgens. Potential differences between the two model androgens were observed in increased expression of cyp17a1 and 11 beta-hydroxysteroid dehydrogenase (11 beta hsd), which were only altered after exposure to DHT and in expression levels of cytochrome P450 11A1 (cyp11a1), which was upregulated by MT but not altered by DHT. Results from this study show both androgens interact at the gonadal level of the hypothalamus-pituitary-gonadal axis and may possess some distinct gene expression impacts. These data strengthen the current research initiatives of establishing in vitro test systems that allow toxic potential of untested chemicals to be predicted from molecular perturbations.
机译:雄激素是一类公认的内分泌扰乱了具有影响水生生物中生殖状态的能力的化合物。目前的研究在24小时的过程中使用了Mummichog(基质脓性脓性碱)睾丸组织的体外暴露于芳族化雄激素17α-甲基上酮(MT)或非芳族化雄激素5α-二氢酮(DHT),以确定是否存在对类体基因表达是差异影响。睾丸组织暴露于10(-12)m,10(-9)m和10(-6)m的雄激素浓度为6,12,18或24小时,之后是类固醇基因的套件,包括甾体急性调节剂使用实时聚合酶链反应量化蛋白质,3β-羟类脱氢酶(3βHSD)和细胞色素P450 17A1(CYP17A1)。两种Androgens都影响了类固醇基因表达,在24小时时间点发生大多数改变。具有最高折叠变化和最短间隔的基因为表达改变,两种Androgens是3个βHSD。在CYP17A1和11β-羟类脱氢酶(11βHSD)的表达增加中观察到两种模型雄激素之间的潜在差异,这仅在暴露于DHT和细胞色素P450 11A1(CYP11A1)的表达水平后仅改变,这是上调的吨但没有改变DHT。本研究的结果显示雄激素在下丘脑 - 垂体 - 性腺轴的性腺水平上相互作用,并且可以具有一些不同的基因表达影响。这些数据强化了建立体外测试系统的当前研究举措,这些举措允许从分子扰动预测未经测试的化学品的毒性潜力。

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