Department of Biochemistry and the Environmental Science Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Fish Physiol Biochem. 2010 Jun;36(2):251-61. doi: 10.1007/s10695-008-9227-0. Epub 2008 May 28.
Environmental estrogen could mimic natural estrogens thereby disrupting the endocrine systems of human and animals. The actions of such endocrine disruptors have been studied mainly on reproduction and development. However, estrogen could also affect the somatotropic axis via multiple targets such as growth hormone (GH). In the present study, two endocrine disruptors were chosen to investigate their effects on the expression level and signal transduction of growth hormone receptor (GHR) in fish. Using real-time PCR, it was found that exposure to both the estrogenic (bisphenol A) and anti-estrogenic (malachite green) compounds could attenuate the expression levels of GHR1 and GHR2 in black seabream (Acanthopagrus schlegeli) hepatocytes. The expression level of IGF-I, the downstream effector of GHR activation in the liver, was decreased by bisphenol A but not by malachite green. Luciferase reporter assay of the beta-casein promoter was used to monitor GHR signaling in transfected cells. In the fish liver cell line Hepa-T1, both GHR1 and GHR2 signaling were attenuated by bisphenol A and malachite green. This attenuation could only occur in the presence of estrogen receptor, indicating that these agents probably produce their actions via the estrogen receptor. Results of the present study demonstrated that estrogenic or anti-estrogenic compounds could down-regulate the somatotropic axis in fish by affecting both the gene expression and signaling of GHR. In view of the increasing prevalence of these compounds in the environment, the impact on fish growth and development both in the wild and in aquaculture would be considerable.
环境雌激素可以模拟天然雌激素，从而扰乱人类和动物的内分泌系统。这些内分泌干扰物的作用主要研究于生殖和发育。然而，雌激素也可以通过多种靶标（如生长激素 (GH)）影响生长激素受体 (GHR) 的体轴。在本研究中，选择了两种内分泌干扰物来研究它们对鱼类生长激素受体 (GHR) 的表达水平和信号转导的影响。使用实时 PCR 发现，暴露于雌激素（双酚 A）和抗雌激素（孔雀石绿）化合物均可降低黑鲷（Acanthopagrus schlegeli）肝细胞中 GHR1 和 GHR2 的表达水平。肝脏中 GHR 激活的下游效应物 IGF-I 的表达水平被双酚 A 降低，但不是被孔雀石绿降低。转染细胞的β-酪蛋白启动子的荧光素酶报告基因检测用于监测 GHR 信号转导。在鱼类肝细胞系 Hepa-T1 中，双酚 A 和孔雀石绿均可减弱 GHR1 和 GHR2 的信号转导。这种衰减只能在存在雌激素受体的情况下发生，表明这些药物可能通过雌激素受体发挥作用。本研究结果表明，雌激素或抗雌激素化合物可以通过影响 GHR 的基因表达和信号转导来下调鱼类的体轴。鉴于这些化合物在环境中越来越普遍，它们对野生和水产养殖鱼类的生长和发育的影响将是相当可观的。
