Department of Biological Sciences, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta, Canada T2N 1N4.
Endocrinology. 2010 Apr;151(4):1668-76. doi: 10.1210/en.2009-1447. Epub 2010 Mar 1.
Estrogens work by binding to and activating specific estrogen receptors (ERs). Although mammals have two major nuclear ER subtypes (ERalpha and ERbeta), three subtypes have been shown in teleost fish (ERalpha, ERbeta-I, and ERbeta-II). 17beta-Estradiol stimulates the production of an egg yolk precursor protein (vitellogenin) in the liver of oviparous species, including the goldfish. However, the functional involvement of the ER subtypes in this process is not fully understood. Here, using primary goldfish hepatocytes, we test the hypothesis that all three ER subtypes are functionally involved in the liver of goldfish by using RNA interference to specifically knock-down the different ER subtypes. The results suggest that ERalpha is induced by estradiol through activation of the ERbeta subtypes. This induction serves to sensitize the liver to further stimulation by estradiol. The knock-down results were supported by use of ER subtype specific antagonists. Sensitization by up-regulation of ERalpha is likely to be important for seasonal spawners such as goldfish, to bring about a change from somatic growth to reproductive development, and vitellogenesis. The novel data presented in this study provide strong support for the hypothesis that the goldfish ER subtypes play functional roles in the regulation of vitellogenin and ERalpha and provide a framework for the better understanding of ER signaling in fish and other vertebrates.
雌激素通过与特定的雌激素受体（ER）结合并激活它们而起作用。虽然哺乳动物有两种主要的核 ER 亚型（ERalpha 和 ERbeta），但在硬骨鱼中已经显示出三种亚型（ERalpha、ERbeta-I 和 ERbeta-II）。17β-雌二醇刺激包括金鱼在内的卵生物种肝脏中卵黄前体蛋白（卵黄蛋白原）的产生。然而，ER 亚型在这个过程中的功能参与尚未完全了解。在这里，我们使用原代金鱼肝细胞，通过使用 RNA 干扰特异性敲低不同的 ER 亚型，测试了所有三种 ER 亚型都在金鱼肝脏中具有功能参与的假设。结果表明，雌二醇通过激活 ERbeta 亚型诱导 ERalpha。这种诱导作用使肝脏对雌二醇的进一步刺激更加敏感。使用 ER 亚型特异性拮抗剂的敲低结果得到了支持。通过 ERalpha 的上调进行的敏化可能对像金鱼这样的季节性产卵者很重要，以使它们从躯体生长转变为生殖发育和卵黄生成。本研究中提出的新数据为金鱼 ER 亚型在卵黄蛋白原和 ERalpha 的调节中发挥功能作用的假设提供了强有力的支持，并为更好地理解鱼类和其他脊椎动物中的 ER 信号提供了框架。
