Musnier Astrid, León Kelly, Morales Julia, Reiter Eric, Boulo Thomas, Costache Vlad, Vourc'h Patrick, Heitzler Domitille, Oulhen Nathalie, Poupon Anne, Boulben Sandrine, Cormier Patrick, Crépieux Pascale
BIOS Group, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 85, F-37380 Nouzilly, France.
Mol Endocrinol. 2012 Apr;26(4):669-80. doi: 10.1210/me.2011-1267. Epub 2012 Mar 1.
FSH is a key hormonal regulator of Sertoli cell secretory activity, required to optimize sperm production. To fulfil its biological function, FSH binds a G protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network ultimately leads to the transcription or down-regulation of numerous genes. In addition, recent evidence has suggested that FSH might also regulate protein translation. However, this point has never been demonstrated conclusively yet. Here we have addressed this issue in primary rat Sertoli cells endogenously expressing physiological levels of FSH-R. We observed that, within 90 min of stimulation, FSH not only enhanced overall protein synthesis in a mammalian target of rapamycin-dependent manner but also increased the recruitment of mRNA to polysomes. m(7)GTP pull-down experiments revealed the functional recruitment of mammalian target of rapamycin and p70 S6 kinase to the 5'cap, further supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E-binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared to play a minor role in translational regulations induced by FSH, in contrast to what is generally observed in response to anabolic factors. This particular regulation of the translational machinery by FSH stimulation might support mRNA-selective translation, as shown here by quantitative RT-PCR amplification of the c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA, in polysomal fractions. These findings add a new level of complexity to FSH biological roles in its natural target cells, which has been underappreciated so far.
促卵泡激素（FSH）是支持细胞分泌活动的关键激素调节因子，对优化精子生成至关重要。为发挥其生物学功能，FSH与一种G蛋白偶联受体——促卵泡激素受体（FSH-R）结合。FSH-R转导的信号网络最终导致众多基因的转录或下调。此外，最近有证据表明FSH也可能调节蛋白质翻译。然而，这一点尚未得到确凿证实。在此，我们在天然表达生理水平FSH-R的原代大鼠支持细胞中解决了这个问题。我们观察到，在刺激90分钟内，FSH不仅以雷帕霉素哺乳动物靶点依赖性方式增强整体蛋白质合成，还增加了mRNA向多核糖体的募集。m(7)GTP下拉实验揭示了雷帕霉素哺乳动物靶点和p70核糖体蛋白S6激酶向5'帽的功能性募集，p70核糖体蛋白S6激酶靶点之一真核起始因子4B磷酸化增强进一步支持了这一点。重要的是，支架蛋白真核起始因子4G也被募集，而真核起始因子4E结合蛋白（真核起始因子4E的通用抑制剂）在FSH诱导的翻译调控中似乎起次要作用，这与对合成代谢因子的一般反应不同。FSH刺激对翻译机制的这种特殊调节可能支持mRNA选择性翻译，如在此通过对多核糖体组分中c-fos和血管内皮生长因子mRNA而非所有FSH靶点mRNA进行定量RT-PCR扩增所显示。这些发现为FSH在其天然靶细胞中的生物学作用增添了新的复杂层面，而这一点迄今尚未得到充分认识。
