title: mRNA-selective translation induced by FSH in primary Sertoli cells.
abstract: 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.
authors.affiliation: BIOS Group, Institut National de la Recherche Agronomique, Unité Mixte de Recherche 85, F-37380 Nouzilly, France.
authors.forename: Astrid
authors.initials: A
authors.lastname: Musnier
authors.forename: Kelly
authors.initials: K
authors.lastname: León
authors.forename: Julia
authors.initials: J
authors.lastname: Morales
authors.forename: Eric
authors.initials: E
authors.lastname: Reiter
authors.forename: Thomas
authors.initials: T
authors.lastname: Boulo
authors.forename: Vlad
authors.initials: V
authors.lastname: Costache
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Domitille
authors.initials: D
authors.lastname: Heitzler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Oulhen
authors.forename: Anne
authors.initials: A
authors.lastname: Poupon
authors.forename: Sandrine
authors.initials: S
authors.lastname: Boulben
authors.forename: Patrick
authors.initials: P
authors.lastname: Cormier
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011132:Polyribosomes / Q000378:metabolism; D061251:Primary Cell Culture; D014176:Protein Biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011962:Receptors, FSH / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C499526:Eif4ebp1 protein, rat; D039603:Eukaryotic Initiation Factor-4G; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D012315:RNA Caps; D012333:RNA, Messenger; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases