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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions
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Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions

机译：乳腺稳态利用上皮紧密连接的血清素能调节

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Homeostatic control of volume within the alveolar spaces of the mammary gland has been proposed to involve a feedback system mediated by serotonin signaling. In this article, we describe some of the mechanisms underlying this feedback based on studies of a human normal mammary epithelial cell line (MCF10A) and mouse mammary epithelium. Mammary serotonin was elevated during lactation and after injection of 5-hydroxytryptophan (5-HTP). The genes encoding the serotonin reuptake transporter (SERT) and the type 7 serotonin receptor (5-HT_7) were expressed in human and mouse mammary epithelial cells, and serotonin caused a concentration-dependent increase of cAMP in MCF10A cells. Mouse and human mammary epithelial cells formed polarized membranes, in which tight junction activity was monitored. Treatment of mammary epithelial membranes with serotonin receptor antagonists increased their transepithelial electrical resistance (TEER). Antagonist and agonist effects on TEER were mediated by receptors on the basolateral face of the membranes. Our results suggest a process in which serotonin accumulates in the interstitial fluid surrounding the mammary secretory epithelium and is detected by 5-HT_7 receptors, whereupon milk secretion is inhibited. One mechanism responsible for this process is serotonin-mediated opening of tight junctions, which dissipates the transepithelial gradients necessary for milk secretion.
机译：已经提出了对乳腺的肺泡腔内的体积进行稳态控制以涉及由5-羟色胺信号传导介导的反馈系统。在本文中，我们基于对人类正常乳腺上皮细胞系（MCF10A）和小鼠乳腺上皮细胞的研究，描述了这种反馈基础。哺乳期间和注射5-羟色氨酸（5-HTP）后，乳腺血清素升高。编码5-羟色胺再摄取转运蛋白（SERT）和7型5-羟色胺受体（5-HT_7）的基因在人和小鼠的乳腺上皮细胞中表达，并且5-羟色胺导致MCF10A细胞中cAMP的浓度依赖性增加。小鼠和人类的乳腺上皮细胞形成了极化的膜，在其中监测了紧密的连接活性。用5-羟色胺受体拮抗剂治疗乳腺上皮膜可增加其跨上皮电阻（TEER）。对TEER的拮抗和激动作用是由膜基底外侧面上的受体介导的。我们的结果表明，血清素在乳腺分泌上皮周围的组织液中蓄积并被5-HT_7受体检测到，从而抑制了乳汁分泌。导致该过程的一种机制是血清素介导的紧密连接的打开，这消除了乳汁分泌所必需的跨上皮梯度。

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