Li Jun, Leghari Imdad H, He Bin, Zeng Weidong, Mi Yuling, Zhang Caiqiao
Key Laboratory of Molecular Animal Nutrition of the Ministry of Education and Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, P.R. China.
Key Laboratory of Molecular Animal Nutrition of the Ministry of Education and Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, P.R. China.
Theriogenology. 2014 Aug;82(3):517-24. doi: 10.1016/j.theriogenology.2014.05.003. Epub 2014 May 20.
Steroid hormones and their receptors play pivotal roles throughout vertebrate reproduction and development. Egg formation in avian species is a prime example. The synthesis of egg yolk proteins by the liver is highly dependent on estrogen. Two major components of the yolk protein precursors, vitellogenin II (VTG II) and very low-density apolipoprotein II (ApoVLDL II), are synthesized in the liver of hens under estrogen stimulation and are subsequently transferred via the blood to the developing oocytes. Estrogen-inducible transcription can be mediated through estrogen receptors (ERs) (ER-α and ER-β) or through G protein-coupled receptor 30 (GPR30), but the exact participation of the individual receptor is not clear. Here, we determine the relative contribution of each transduction pathway in the synthesis of VTG II and ApoVLDL II in the hepatocytes by using selective compounds that are known to specifically interact with each of the ERs and GPR30. 17β-Estradiol and propyl pyrazole triol (PPT, ER-α agonist) induced increase in VTG II and ApoVLDL II mRNA expressions in a dose-dependent manner. A high concentration of diarylpropionitrile (DPN, which preferentially motivates ER-β) slightly stimulated the expression of VTG II and ApoVLDL II mRNAs. However, G-1 (a GPR30 agonist) failed to display any stimulating role. Methyl-piperidino-pyrazole (a highly selective ER-α antagonist) fully blocked the expression of both yolk precursors, which were upregulated by 17β-estradiol, PPT, and DPN. Considering that DPN can also provoke the action of ER-α at high concentration, this excludes the participation of ER-β and supports the role of ER-α. The aforementioned results indicate that estrogen stimulates the expression of VTG II and ApoVLDL II mRNAs predominantly through ER-α in the chicken liver.
类固醇激素及其受体在整个脊椎动物的繁殖和发育过程中发挥着关键作用。鸟类的卵子形成就是一个典型例子。肝脏中卵黄蛋白的合成高度依赖雌激素。卵黄蛋白前体的两个主要成分，即卵黄生成素II（VTG II）和极低密度载脂蛋白II（ApoVLDL II），在雌激素刺激下在母鸡肝脏中合成，随后通过血液转移到发育中的卵母细胞。雌激素诱导的转录可通过雌激素受体（ERs）（ER-α和ER-β）或通过G蛋白偶联受体30（GPR30）介导，但各个受体的确切参与情况尚不清楚。在这里，我们通过使用已知能与每种ERs和GPR30特异性相互作用的选择性化合物，确定了每条转导途径在肝细胞中VTG II和ApoVLDL II合成中的相对贡献。17β-雌二醇和丙基吡唑三醇（PPT，ER-α激动剂）以剂量依赖性方式诱导VTG II和ApoVLDL II mRNA表达增加。高浓度的二芳基丙腈（DPN，优先激活ER-β）轻微刺激了VTG II和ApoVLDL II mRNA的表达。然而，G-1（一种GPR30激动剂）未能显示出任何刺激作用。甲基哌啶基吡唑（一种高度选择性的ER-α拮抗剂）完全阻断了两种卵黄前体的表达，这两种前体在17β-雌二醇、PPT和DPN作用下被上调。考虑到DPN在高浓度下也能激发ER-α的作用，这排除了ER-β的参与并支持了ER-α的作用。上述结果表明，雌激素主要通过鸡肝脏中的ER-α刺激VTG II和ApoVLDL II mRNA的表达。
