Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy.
Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells during pregnancy.
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DOI：
10.1007/s00125-010-1913-7
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发表时间：
2010-12
期刊：
影响因子：
8.2
通讯作者：
Schuit, F.
中科院分区：
文献类型：
--
作者：
Schraenen, A.;Lemaire, K.;de Faudeur, G.;Hendrickx, N.;Granvik, M.;Van Lommel, L.;Mallet, J.;Vodjdani, G.;Gilon, P.;Binart, N.;in't Veld, P.;Schuit, F.
关键词：
需要功能性β细胞群的上调以匹配妊娠期间母亲和胎儿的生理需求。这种增加依赖于胎盘催乳素（PL）和催乳素受体，但这些事件的机制仅部分了解。我们研究了怀孕期间小鼠胰岛的mRNA表达谱，以更好地了解这些变化。通过微阵列和定量RT-PCR离体测量RNA表达。通过体外模型扩展了体内观察，在体外模型中将绵羊PL添加到培养的小鼠胰岛和MIN 6细胞中。编码5-羟色胺生物合成的限速酶色氨酸羟化酶（TPH），即Tph 1和Tph 2的两种亚型的mRNA在妊娠期间被强烈诱导（倍数变化25至200倍）。通过将胰岛或MIN 6细胞暴露于绵羊PL 24小时来模拟这种诱导，并且依赖于Janus激酶2和信号转导子和转录激活子5。与Tph 1 mRNA和蛋白诱导平行，胰岛5-羟色胺含量增加到比基础高200倍的峰值水平。有趣的是，只有一个亚群的β细胞是阳性的，在体外和体内。在妊娠胰岛和PL处理的MIN 6细胞中储存的血清素池被迅速释放（每2小时更新一次）。在妊娠期间，小鼠胰岛β细胞亚群中发生非常强烈的催乳素依赖性5-羟色胺生物合成上调。由于新形成的5-羟色胺迅速释放，这种催乳素诱导的β细胞功能可能服务于局部或内分泌任务，其性质仍有待确定。本文的在线版本（doi：10.1007/s 00125 -010-1913-7）包含补充材料，可供授权用户使用。
Upregulation of the functional beta cell mass is required to match the physiological demands of mother and fetus during pregnancy. This increase is dependent on placental lactogens (PLs) and prolactin receptors, but the mechanisms underlying these events are only partially understood. We studied the mRNA expression profile of mouse islets during pregnancy to gain a better insight into these changes. RNA expression was measured ex vivo via microarrays and quantitative RT-PCR. In vivo observations were extended by in vitro models in which ovine PL was added to cultured mouse islets and MIN6 cells. mRNA encoding both isoforms of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase (TPH), i.e. Tph1 and Tph2, were strongly induced (fold change 25- to 200-fold) during pregnancy. This induction was mimicked by exposing islets or MIN6 cells to ovine PLs for 24 h and was dependent on janus kinase 2 and signal transducer and activator of transcription 5. Parallel to Tph1 mRNA and protein induction, islet serotonin content increased to a peak level that was 200-fold higher than basal. Interestingly, only a subpopulation of the beta cells was serotonin-positive in vitro and in vivo. The stored serotonin pool in pregnant islets and PL-treated MIN6 cells was rapidly released (turnover once every 2 h). A very strong lactogen-dependent upregulation of serotonin biosynthesis occurs in a subpopulation of mouse islet beta cells during pregnancy. Since the newly formed serotonin is rapidly released, this lactogen-induced beta cell function may serve local or endocrine tasks, the nature of which remains to be identified. The online version of this article (doi:10.1007/s00125-010-1913-7) contains supplementary material, which is available to authorised users.
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影响因子：
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