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首页> 外文期刊>Environmental toxicology and chemistry >Time-dependent Transcriptional Profiles Of Genes Of The Hypothalamic-pituitary-gonadal Axis In Medaka (oryzias Latipes) Exposed To Fadrozole And 17β-trenbolone
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Time-dependent Transcriptional Profiles Of Genes Of The Hypothalamic-pituitary-gonadal Axis In Medaka (oryzias Latipes) Exposed To Fadrozole And 17β-trenbolone

机译：暴露于法得唑和17β-群勃龙中的Medaka（oryzias Latipes）下丘脑-垂体-性腺轴基因的时间依赖性转录谱

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Both the anabolic androgen 17β-trenbolone (TRB) and the aromatase inhibitor fadrozole (FAD) can cause decreased plasma concentrations of estrogen (E2) and reduce fecundity of fish. However, the underlying mechanisms and the molecular pathways involved are largely unknown. The present study was designed to assess time-dependent effects of FAD and TRB on the transcriptional responses of the hypothalamic-pituitary-gonadal (HPG) axis of Japanese medaka (Oryzias latipes). Fourteen-week-old Japanese medaka were exposed to 50 μg FAD/L or 2 μg TRB/L in a 7-d static renewal test, and the expression profiles of 36 HPG axis genes were measured by means of a medaka HPG real-time reverse-transcription polymerase chain reaction array after 8 h, 32 h, or 7 d of exposure. Exposure to TRB or FAD caused lesser fecundity of Japanese medaka and down-regulated transcription of vitellogenin and choriogenin (CHG) gene expression in the liver of females. Exposure to FAD for 8 h resulted in an 8-fold and 71-fold down-regulation of expression of estrogen receptor α and choriogenin L (CHG L), respectively, in female liver. 17β-Trenbolone caused similar down-regulation of these genes, but the effects were not observed until 32 h of exposure. These results support the hypothesis that FAD reduces plasma E2 more quickly by inhibiting aromatase enzyme activity than does TRB, which inhibits the production of the E2 precursor testosterone. Exposure to FAD and TRB resulted in rapid (after 8 h) down-regulation of luteinizing hormone receptor and low-density-lipoprotein receptor in the testis to compensate for excessive androgen levels. Overall, the molecular responses observed in the present study differentiate the mechanisms of the reduced fecundity by TRB and FAD.
机译：合成代谢雄激素17β-群勃龙（TRB）和芳香酶抑制剂Fadrozole（FAD）均可导致血浆雌激素（E2）浓度降低并降低鱼类的繁殖力。但是，所涉及的潜在机制和分子途径在很大程度上尚不清楚。本研究旨在评估FAD和TRB对日本（Oryzias latipes）的下丘脑-垂体-性腺（HPG）轴的转录反应的时间依赖性作用。在7天的静态更新测试中，将14周大的日本medaka暴露于50μgFAD / L或2μgTRB / L，并通过medaka HPG实时测量36个HPG轴基因的表达谱暴露8 h，32 h或7 d后进行逆转录聚合酶链反应阵列。暴露于TRB或FAD会降低日本的繁殖力，并降低女性肝脏中卵黄蛋白原和绒毛膜促性腺激素（CHG）基因表达的转录。暴露于FAD 8 h导致雌性肝中雌激素受体α和胆囊生成素L（CHG L）的表达分别下调8倍和71倍。 17β-群勃龙引起这些基因的类似下调，但直到暴露32 h才观察到这种作用。这些结果支持以下假说：与TRB相比，FAD通过抑制芳香酶的活性来更快地降低血浆E2，而TRB则抑制了E2前体睾丸激素的产生。暴露于FAD和TRB会导致睾丸中黄体生成激素受体和低密度脂蛋白受体快速（8小时后）下调，以补偿雄激素水平过高。总的来说，在本研究中观察到的分子反应区分了TRB和FAD降低繁殖力的机制。

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