Molecular Cloning, Characterization, and Evolutionary Analysis of Estrogen Receptors from Phylogenetically Ancient Fish
Molecular Cloning, Characterization, and Evolutionary Analysis of Estrogen Receptors from Phylogenetically Ancient Fish
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DOI：
10.1210/en.2008-0670
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发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Iguchi, Taisen
中科院分区：
文献类型：
--
作者：
Katsu, Yoshinao;Kohno, Satomi;Iguchi, Taisen
在许多脊椎动物的关键发育阶段，雌激素是卵巢分化所必需的，它们促进成年雌性生殖系统的生长和分化。为了了解脊椎动物雌激素受体（ESRs）的进化，并评估雌激素受体-配体相互作用的遗传古老的鱼类，我们使用PCR技术分离的cDNA编码ESRs从肺鱼，鲟鱼，和雀鳝。序列分析表明，这些鱼类有两个ESRs，ESR 1（ER α）和ESR 2（ER β），如以前报道的其他脊椎动物物种，但第二种类型的ESR 2（ER β 2）没有发现，已报告在一些硬骨鱼。ESR序列的系统发育分析表明，肺鱼的ESR被归类为四足动物的ESR组，而不是与硬骨鱼的ESR是从雀鳝和鲟鱼的ESR。使用哺乳动物细胞的瞬时转染试验，ESR蛋白从这三个古老的鱼类显示雌激素依赖性激活的转录从雌激素反应元件包含启动子。我们还研究了o，p '-二氯二苯基三氯乙烷（o，p'-DDT）和p，p '-DDT及其常见代谢物p，p'-二氯二苯基乙烯（p，p '-DDE）对这些鱼的雌激素受体的雌激素样作用。肺鱼ESR 1对DDT/DDE的敏感性低于其它两种鱼。肺鱼ESR 1对这些农药的反应与从蝾螈ESR 1获得的模式相似。这些数据提供了一个基本的工具，使未来的研究检查受体-配体的相互作用和内分泌干扰机制在三个物种的遗传古老的鱼，也扩大了我们的知识进化。（内分泌学149：6300-6310，2008）
Estrogens are necessary for ovarian differentiation during a critical developmental stage in many vertebrates, and they promote the growth and differentiation of the adult female reproductive system. To understand the evolution of vertebrate estrogen receptors (ESRs) and to evaluate estrogen receptor-ligand interactions in phylogenetically ancient fish, we used PCR techniques to isolate the cDNA encoding ESRs from lungfish, sturgeon, and gar. Sequence analyses indicate that these fishes have two ESRs, ESR1 (ER alpha) and ESR2 ( ER beta),as previously reported for other vertebrate species, but a second type of ESR2 (ER beta 2) was not found as has been reported in a number of teleost fishes. Phylogenetic analysis of the ESR sequences indicated that the lungfish ESRs are classified to the tetrapod ESR group, not with the teleost fish ESRs as are the ESRs from gar and sturgeon. Using transient transfection assays of mammalian cells, ESR proteins from these three ancient fishes displayed estrogen-dependent activation of transcription from an estrogen-responsive-element containing promoter. We also examined the estrogenic potential of o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) and p,p'-DDT as well as one of its common metabolites, p,p'-dichloro-diphenyl-ethylene (p,p'-DDE) on the ESRs from these fishes. Lungfish ESR1 was less sensitive to DDT/DDE than the ESR1 from the other two fishes. The response of lungfish ESR1 to these pesticides is similar to the pattern obtained from salamander ESR1. These data provide a basic tool allowing future studies examining the receptor-ligand interactions and endocrine-disrupting mechanisms in three species of phylogenetically ancient fish and also expands our knowledge evolution. ( Endocrinology 149: 6300-6310, 2008)