Estrogen-Dependent Transactivation of Amphioxus Steroid Hormone Receptor via Both Estrogen and Androgen Response Elements
Estrogen-Dependent Transactivation of Amphioxus Steroid Hormone Receptor via Both Estrogen and Androgen Response Elements
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DOI：
10.1210/en.2009-0766
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发表时间：
2010-02-01
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;Kubokawa, Kaoru;Iguchi, Taisen
雌激素是大多数脊椎动物在关键发育窗口期卵巢分化所必需的，并促进成年雌性生殖系统的生长和分化。雌激素作用主要通过雌激素受体（ER）介导，ER是配体激活的转录因子。为了了解性类固醇激素受体的分子进化，我们从日本文昌鱼Branchiostoma belcheri分离编码两种类固醇受体的cDNA：ER直系同源物和酮类固醇受体（SR）直系同源物。报告基因分析表明，SR直系同源物具有类似于脊椎动物ER的分子功能。令人惊讶的是，ER直系同源物是SR介导的转录的雌激素不敏感阻遏物。此外，我们发现SR直系同源物可以结合到雌激素反应元件（ERE）和雄激素反应元件（战神），并介导转录激活雌激素通过这两种类型的元素。我们的研究结果表明，祖先SR，而不是ER，可以结合雌酮，并诱导ERE和ARE依赖的反式激活，它获得了由酮类固醇调节的能力，并识别ARE特异性无颌脊椎动物分裂之前。这些结果突出了内分泌系统进化研究的比较实验方法的重要性。（内分泌学151：639-648，2010）
Estrogens are necessary for ovarian differentiation during critical developmental windows in most vertebrates and promote the growth and differentiation of the adult female reproductive system. Estrogen actions are largely mediated through the estrogen receptors (ERs), which are ligand-activated transcription factors. To understand the molecular evolution of sex steroid hormone receptors, we isolated cDNAs encoding two steroid receptors from Japanese amphioxus, Branchiostoma belcheri: an ER ortholog and a ketosteroid receptor (SR) ortholog. Reporter gene assays revealed that the SR ortholog has molecular functions similar to those of the vertebrate ER. Surprisingly, the ER ortholog is an estrogen-insensitive repressor of SR-mediated transcription. Furthermore, we found that the SR ortholog can bind to both estrogen-responsive elements (EREs) and androgen-responsive elements (AREs) and mediates transcriptional activation by estrogens through both types of elements. Our findings suggest that the ancestral SR, but not ER, could bind estrone and induce the ERE- and ARE-dependent transactivation and that it gained the ability to be regulated by ketosteroid and recognize ARE specifically before jawless vertebrates split. These results highlight the importance of comparative experimental approaches for the evolutionary study of endocrine systems. (Endocrinology 151: 639-648, 2010)