Estrogenic potency of MC-LR is induced via stimulating steroidogenesis: In vitro and in vivo evidence.
Estrogenic potency of MC-LR is induced via stimulating steroidogenesis: In vitro and in vivo evidence.
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MC-LR 的雌激素效力是通过刺激类固醇生成诱导的：体外和体内证据
DOI：
10.1016/j.envpol.2018.04.140
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Hou J;Su Y;Lin W;Guo H;Li L;Anderson DM;Li D;Tang R;Chi W;Zhang X
水溶性微囊藻毒素-LR（MC-LR）已被报道会干扰性激素，但其雌激素效力仍存在争议。我们推测MC-LR可能通过干扰性激素合成而诱导雌激素样作用，并通过体外和体内试验验证了这一假设。48 h后，在H295 R细胞中评估MC-LR（1、10、100、500、1000和5000 μg/L）对类固醇生成的影响。17β-雌二醇（E2）和睾酮（T）含量呈非剂量依赖性增加，与类固醇基因表达呈正相关。在体内试验中，将成年雄性斑马鱼暴露于0.3、1、3、10和30 μg/L的MC-LR中30 d。同样，睾丸中的E2和T含量增加，伴随着类固醇基因的广泛上调，特别是cyp 19 a。睾丸中精子细胞的比例下降。在肝脏中，vtg 1基因显著上调，而雌激素受体（ER）的转录和蛋白水平下降。这些结果表明，MC-LR诱导非剂量依赖性雌激素效应在环境浓度，这可能是由于类固醇激素刺激通过非ER介导的途径。我们的研究结果支持MC-LR的风险评估从传统的毒性到雌激素风险的范式转变，特别是在低浓度下，并强调了开花地区野生动物雄性生殖能力的潜在威胁。MC-LR通过在体外和体内条件下刺激类固醇生成诱导非剂量依赖性雌激素效应。
Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes. In the in vivo assay, adult male zebrafish were exposed to 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d. Similarly, E2 and T contents in the testis were increased, accompanied by extensive up-regulation of steroidogenic genes, especially cyp19a. Meanwhile, the percentage of spermatid in the testis declined. In the liver, the vtg1 gene was significantly up-regulated while both the transcriptional and protein levels of the estrogenic receptor (ER) declined. These results indicate that MC-LR induced non-dose-dependent estrogenic effects at environmental concentrations, which may result from steroidogenesis stimulation via a non-ER-mediated pathway. Our findings support a paradigm shift in the risk assessment of MC-LR from traditional toxicity to estrogenic risk, particularly at low concentrations, and emphasize the potential threat to the male reproductive capacity of wildlife in bloom areas. MC-LR induced non-dose-dependent estrogenic effects via stimulating steroidogenesis in both in vitro and in vivo conditions.
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影响因子：
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作者：
Liu W;Chen C;Chen L;Wang L;Li J;Chen Y;Jin J;Kawan A;Zhang X
通讯作者：
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DOI：
10.1530/jrf.0.1140131
发表时间：
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