Shved Natallia, Berishvili Giorgi, Baroiller Jean-François, Segner Helmut, Reinecke Manfred
Division of Neuroendocrinology, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Toxicol Sci. 2008 Nov;106(1):93-102. doi: 10.1093/toxsci/kfn150. Epub 2008 Jul 27.
The aim of this study was to evaluate whether effects of environmental estrogens on fish growth and reproduction may be mediated via modulating the growth hormone (GH)/insulin-like growth factor I (IGF-I) system. To this end, developing male and female monosex populations of tilapia were exposed to 17alpha-ethinylestradiol (EE2) at 5 and 25 ng EE2/l water from 10-day postfertilization (DPF) until 100 DPF. Under exposure to both EE2 concentrations, sex ratio shifted toward more females and body length, and weight were significantly reduced in males. The growth-reducing effect was associated with significant changes in hepatic IGF-I expression, both in males and females and with significant alterations of IGF-I mRNA and GH mRNA in the brain. The changes in IGF-I and GH mRNA were accompanied by altered estrogen receptor alpha (ERalpha) expression in brain and liver. These findings point to an influence of estrogenic exposure on the endocrine GH/IGF-I axis. In addition, the EE2 treatment resulted in significant changes of ERalpha and IGF-I expression in ovaries and testis, suggesting that the estrogens interact not only with the endocrine but also with the autocrine/paracrine part of the IGF-I system. Overall, our results provide evidence that EE2 at environmentally relevant concentrations is able to interfere with the GH/IGF-I system in bony fish and that the impairing effects of estrogens reported on fish growth and reproductive functions may rather result from a cross talk between the sex steroid and the IGF-I system than be toxicological.
本研究的目的是评估环境雌激素对鱼类生长和繁殖的影响是否可能通过调节生长激素(GH)/胰岛素样生长因子I(IGF-I)系统来介导。为此,从受精后10天(DPF)至100 DPF,将发育中的罗非鱼单性种群暴露于5和25 ng EE2/L水中的17α-乙炔雌二醇(EE2)。在两种EE2浓度暴露下,性别比例向雌性偏移,雄性的体长和体重显著降低。生长抑制作用与肝脏中IGF-I表达的显著变化有关,在雄性和雌性中均如此,并且与大脑中IGF-I mRNA和GH mRNA的显著改变有关。IGF-I和GH mRNA的变化伴随着大脑和肝脏中雌激素受体α(ERα)表达的改变。这些发现表明雌激素暴露对内分泌GH/IGF-I轴有影响。此外,EE2处理导致卵巢和睾丸中ERα和IGF-I表达的显著变化,表明雌激素不仅与内分泌相互作用,还与IGF-I系统的自分泌/旁分泌部分相互作用。总体而言,我们的结果提供了证据,表明环境相关浓度的EE2能够干扰硬骨鱼的GH/IGF-I系统,并且报道的雌激素对鱼类生长和生殖功能的损害作用可能更多地源于性类固醇和IGF-I系统之间的相互作用,而非毒理学作用。