Stimulation of serotonergic 5-HT2A receptor signaling increases placental aromatase (CYP19) activity and expression in BeWo and JEG-3 human choriocarcinoma cells
Stimulation of serotonergic 5-HT2A receptor signaling increases placental aromatase (CYP19) activity and expression in BeWo and JEG-3 human choriocarcinoma cells
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DOI：
10.1016/j.placenta.2011.06.003
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发表时间：
2011-09-01
期刊：
影响因子：
3.8
通讯作者：
Sanderson, J. T.
中科院分区：
文献类型：
--
作者：
Klempan, T.;Hudon-Thibeault, A. -A.;Sanderson, J. T.
众所周知，血清素可以影响性激素（如雌激素）的产生和功能。雌激素对维持妊娠和调节胎盘和胎儿发育至关重要。妊娠期间控制雌激素合成的关键酶是胎盘芳香化酶（CYP19）。为了更好地了解胎盘芳香化酶的调节，本研究确定了血清素是否参与了该酶的调节。以BeWo和JEG-3绒毛膜癌细胞作为人胎盘滋养细胞模型，评价血清素和选择性5-HT2A受体激动剂对CYP19活性和表达的影响。5-羟色胺和选择性5-HT2A受体激动剂以及PKC激活增加了BeWo和JEG-3细胞中芳香化酶的活性和表达。地塞米松通过激活某些组织的JAK/STAT来调节芳香化酶的表达，但没有效果。5-HT2A受体增加CYP19基因转录和PKC刺激通过激活胎盘1.1芳香化酶启动子介导。本研究表明，血清素能系统调节胎盘芳香化酶的表达，从而改变滋养细胞中雌激素的生物合成。未来对胎盘中5 -羟色胺-雌激素相互作用的详细研究对于进一步了解5 -羟色胺在妊娠和胎儿发育过程中的内分泌、旁分泌和自分泌作用至关重要。(C) 2011 Elsevier Ltd.版权所有。
It is known that serotonin can influence the production and function of sex hormones, such as estrogens. Estrogens are critical for maintenance of pregnancy and regulate placental and fetal development. The key enzyme controlling estrogens synthesis during pregnancy is placental aromatase (CYP19). To better understand the regulation of placental aromatase, this study determined whether serotonin is involved in the regulation of this enzyme. BeWo and JEG-3 choriocarcinoma cells were used as models of the human placental trophoblast to evaluate the effects of serotonin and selective 5-HT2A receptor agonists on CYP19 activity and expression. Serotonin and selective 5-HT2A receptor agonists as well as PKC activation increased aromatase activity and expression in BeWo and JEG-3 cells. Dexamethasone, which regulates aromatase expression via JAK/STAT activation in certain tissues, had no effect. Increased CYP19 gene transcription by 5-HT2A receptor and PKC stimulation was mediated by activation of the placental 1.1 aromatase promoter. This study shows that the serotonergic system modulates placental aromatase expression, which would result in altered estrogens biosynthesis in trophoblast cells. Future detailed studies of serotonin-estrogen interactions in placenta are crucial for an improved understanding of the endo-, para- and autocrine role of serotonin during pregnancy and fetal development. (C) 2011 Elsevier Ltd. All rights reserved.