Abstract
Follicle-stimulating hormone (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 signalling 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 minutes of stimulation, FSH not only enhanced overall protein synthesis in a mammalian Target Of Rapamycin (mTOR)-dependent manner, but also increased the recruitment of mRNA to polysomes. m7GTP pull-down experiments revealed the functional recruitment of mTOR and p70 S6 kinase (p70S6K) to the 5’cap, further supported by the enhanced phosphorylation of one of p70S6K targets, the eukaryotic initiation factor 4B (eIF4B). Importantly, the scaffolding eukaryotic initiation factor 4G (eIF4G) was also recruited, whereas eukaryotic initiation factor 4E (eIF4E)-binding protein (4E-BP1), the eIF4E 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 qRT-PCR amplification of the c-fos and VEGF 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.
