Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta.
Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta.
复制标题
雌激素受体β对小鼠心脏脂质运载蛋白型前列腺素D合酶的特异性调节。
作者：
M. Otsuki;Hui Gao;K. Dahlman;C. Ohlsson;N. Eguchi;Y. Urade;J. Gustafsson
雌激素在心血管系统中具有重要的生理作用。我们使用DNA微阵列技术来研究雌激素在心脏中作用的分子机制，并确定新的雌激素调节基因。在这项调查中，我们确定了基因的调节慢性雌激素治疗小鼠心脏。我们提出了我们的这些基因之一，脂质运载蛋白型前列腺素D合成酶（L-PGDS）的详细特征。北方和Western印迹分析表明，急性和慢性雌激素处理诱导L-PGDS。北方印迹分析，使用雌激素受体（ER）破坏的小鼠，表明L-PGDS是特异性诱导ER β在体内。在ER β选择性调节的进一步支持，我们确定了一个功能性的雌激素反应元件的L-PGDS启动子，其活性上调ER β，但不是由ER α。我们证明，一个核苷酸的变化（A到C）在L-PGDS雌激素反应元件影响受体的选择性。
Estrogens have important physiological roles in the cardiovascular system. We use DNA microarray technology to study the molecular mechanism of estrogen action in the heart and to identify novel estrogen-regulated genes. In this investigation we identify genes that are regulated by chronic estrogen treatment of mouse heart. We present our detailed characterization of one of these genes, lipocalin-type prostaglandin D synthase (L-PGDS). Northern and Western blot analysis revealed that L-PGDS was induced both by acute and chronic estrogen treatment. Northern blot analysis, using estrogen receptor (ER)-disrupted mice, suggests that L-PGDS is specifically induced by ERbeta in vivo. In further support of ERbeta-selective regulation, we identify a functional estrogen-responsive element in the L-PGDS promoter, the activity of which is up-regulated by ERbeta, but not by ERalpha. We demonstrate that a one-nucleotide change (A to C) in the L-PGDS estrogen-responsive element affects receptor selectivity.
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