Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone
Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone
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DOI：
10.1210/me.14.11.1811
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发表时间：
2000-11-01
影响因子：
--
通讯作者：
Lawson, MA
中科院分区：
文献类型：
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作者：
Sosnowski, R;Mellon, PL;Lawson, MA
神经肽GnRH是哺乳动物生殖功能的中枢调节剂，由分散的下丘脑神经分泌神经元产生。GnRH的主要作用是通过垂体前叶的促性腺细胞调节促性腺激素、LH和FSH的释放。通过小鼠垂体促性腺激素细胞α T3-1细胞的培养细胞模型，我们发现GnRH刺激α T3-1细胞导致帽依赖性mRNA翻译的增加。GnRH受体激活通过mRNA翻译起始的调节因子，真核翻译起始因子4e结合蛋白，称为4EBP或PHAS（蛋白质、热和酸稳定），导致蛋白质合成增加。虽然GnRH受体是G蛋白连接受体视紫红质样家族的成员，但我们发现翻译的激活是通过先前描述的受体酪氨酸激酶的信号通路进行的。GnRH对翻译的刺激依赖于蛋白激酶C和Ras，并且对雷帕霉素敏感。此外，GnRH还可能调节α T3-1细胞的细胞周期。调节蛋白质合成和细胞周期的信号通路的激活表明，GnRH除了指导促性腺激素的释放外，还可能在维持垂体促性腺激素群体中发挥重要作用。
The neuropeptide GnRH is a central regulator of mammalian reproductive function produced by a dispersed population of hypothalamic neurosecretory neurons. The principal action of GnRH is to regulate release of the gonadotropins, LH and FSH, by the gonadotrope cells of the anterior pituitary. Using a cultured cell model of mouse pituitary gonadotrope cells, alpha T3-1 cells, we present evidence that GnRH stimulation of alpha T3-1 cells results in an increase in cap-dependent mRNA translation. GnRH receptor activation results in increased protein synthesis through a regulator of mRNA translation initiation, eukaryotic translation initiation factor 4E-binding protein, known as 4EBP or PHAS (protein, heat, and acid stable). Although the GnRH receptor is a member of the rhodopsin-like family of G protein-linked receptors, we show that activation of translation proceeds through a signaling pathway previously described for receptor tyrosine kinases. Stimulation of translation by GnRH is protein kinase C and Ras dependent and sensitive to rapamycin. Furthermore, GnRH may also regulate the cell cycle in alpha T3-1 cells. The activation of a signaling pathway that regulates both protein synthesis and cell cycle suggests that GnRH may have a significant role in the maintenance of the pituitary gonadotrope population in addition to directing the release of gonadotropins.