Activation of D2 dopamine receptors inhibits estrogen response element-mediated estrogen receptor transactivation in rat pituitary lactotrophs
Activation of D2 dopamine receptors inhibits estrogen response element-mediated estrogen receptor transactivation in rat pituitary lactotrophs
复制标题
DOI：
10.1016/j.mce.2013.05.011
复制
发表时间：
2013-08-15
影响因子：
4.1
通讯作者：
Arita, Jun
中科院分区：
文献类型：
--
作者：
Ishida, Maho;Mitsui, Tetsuo;Arita, Jun
雌激素和多巴胺是垂体催乳细胞内分泌功能的主要对立调节因子。多巴胺抑制雌激素诱导的催乳素合成和分泌的变化以及催乳细胞增殖。我们研究了多巴胺能刺激对雌激素诱导的原代培养大鼠催乳细胞功能变化的抑制作用的机制。多巴胺能激动剂溴隐亭（BC）抑制17 β-雌二醇刺激的催乳细胞增殖、催乳素启动子活性和一些雌激素应答基因的mRNA表达。在泌乳素富集的垂体细胞中，BC处理抑制了雌激素反应元件（ERE）DNA序列介导的雌激素受体（ER）转录活性。使用催乳素特异性ERE转录测定，我们发现BC对ERE介导的ER转录活性的抑制部分涉及D-2多巴胺受体介导的、百日咳毒素敏感的G蛋白偶联的、CAMP/蛋白激酶A依赖的信号传导。BC处理对ER α的细胞浓度或其Ser-118磷酸化状态没有影响。在GH（4）ZR（7）细胞（一种表达D-2多巴胺受体的体乳细胞系）中也发现了BC的类似转录抑制作用。这些结果表明，D-2多巴胺受体的激活抑制雌激素依赖性催乳功能的一部分，通过衰减ERE介导的ER反式激活。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Estrogen and dopamine are major opposing regulators of the endocrine functions of pituitary lactotrophs. Dopamine inhibits estrogen-induced changes in the synthesis and secretion of prolactin, and lactotroph proliferation. We studied the mechanism of the inhibitory effects of dopaminergic stimulation on estrogen-induced functional changes of rat lactotrophs in primary culture. The dopaminergic agonist, bromocriptine (BC), suppressed 17 beta-estradiol-stimulated lactotroph proliferation, prolactin promoter activity, and mRNA expression of some estrogen-responsive genes. In lactotroph-enriched pituitary cells, BC treatment inhibited the estrogen response element (ERE) DNA sequence-mediated estrogen receptor (ER) transcriptional activity. Using a lactotroph-specific ERE transcriptional assay, we found that BC inhibition of the ERE-mediated ER transcriptional activity partly involved D-2 dopamine receptor-mediated, pertussis toxin-sensitive G protein-coupled, CAMP/protein kinase A-dependent signaling. BC treatment had no effect on the cellular concentration of ER alpha or its phosphorylation status at Ser-118. Similar transcriptional inhibition by BC was also found in GH(4)ZR(7) cells, a D-2 dopamine receptor-expressing somatomammotrophic cell line. These results suggest that activation of the D-2 dopamine receptors inhibits estrogen-dependent lactotroph functions in part via attenuation of ERE-mediated ER transactivation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.