Shved Natallia, Berishvili Giorgi, D'Cotta Helena, Baroiller Jean-François, Segner Helmut, Eppler Elisabeth, Reinecke Manfred
Division of Neuroendocrinology, Institute of Anatomy, University of Zürich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland.
J Endocrinol. 2007 Dec;195(3):513-23. doi: 10.1677/JOE-07-0295.
Growth and sexual development are closely interlinked in fish; however, no reports exist on potential effects of estrogen on the GH/IGF-I-axis in developing fish. We investigate whether estrogen exposure during early development affects growth and the IGF-I system, both at the systemic and tissue level. Tilapia were fed from 10 to 40 days post fertilization (DPF) with 17alpha-ethinylestradiol (EE(2)). At 50, 75, 90, and 165 DPF, length, weight, sex ratio, serum IGF-I (RIA), pituitary GH mRNA and IGF-I, and estrogen receptor alpha (ERalpha) mRNA in liver, gonads, brain, and gills (real-time PCR) were determined and the results correlated to those of in situ hybridization for IGF-I. Developmental exposure to EE(2) had persistent effects on sex ratio and growth. Serum IGF-I, hepatic IGF-I mRNA, and the number of IGF-I mRNA-containing hepatocytes were significantly decreased at 75 DPF, while liver ERalpha mRNA was significantly induced. At 75 DPF, a transient decline of IGF-I mRNA and a largely reduced number of IGF-I mRNA-containing neurons were observed in the female brain. In both sexes, pituitary GH mRNA was significantly suppressed. A transient downregulation of IGF-I mRNA occurred in ovaries (75 DPF) and testes (90 DPF). In agreement, in situ hybridization revealed less IGF-I mRNA signals in granulosa and germ cells. Our results show for the first time that developmental estrogen treatment impairs GH/IGF-I expression in fish, and that the effects persist. These long-lasting effects both seem to be exerted indirectly via inhibition of pituitary GH and directly by suppression of local IGF-I in organ-specific cells.
在鱼类中，生长与性发育紧密相连；然而，目前尚无关于雌激素对发育中鱼类生长激素/胰岛素样生长因子-I轴（GH/IGF-I轴）潜在影响的报道。我们研究了鱼类早期发育阶段暴露于雌激素是否会在全身和组织水平上影响生长及胰岛素样生长因子-I（IGF-I）系统。罗非鱼在受精后10至40天（DPF）期间投喂17α-乙炔雌二醇（EE₂）。在50、75、90和165 DPF时，测定鱼的体长、体重、性别比例、血清IGF-I（放射免疫分析）、垂体生长激素（GH）mRNA以及肝脏、性腺、脑和鳃中IGF-I和雌激素受体α（ERα）mRNA（实时定量PCR），并将结果与IGF-I原位杂交结果进行关联分析。发育阶段暴露于EE₂对性别比例和生长有持续影响。在75 DPF时，血清IGF-I、肝脏IGF-I mRNA以及含IGF-I mRNA的肝细胞数量显著减少，而肝脏ERα mRNA显著增加。在75 DPF时，雌性脑中观察到IGF-I mRNA短暂下降且含IGF-I mRNA的神经元数量大幅减少。在两性中，垂体GH mRNA均受到显著抑制。卵巢（75 DPF）和睾丸（90 DPF）中出现IGF-I mRNA的短暂下调。同样，原位杂交显示颗粒细胞和生殖细胞中IGF-I mRNA信号减少。我们的结果首次表明，发育阶段雌激素处理会损害鱼类GH/IGF-I的表达，且这种影响会持续存在。这些长期影响似乎既通过抑制垂体GH间接发挥作用，也通过抑制器官特异性细胞中的局部IGF-I直接发挥作用。
