FSH-stimulated PTEN activity accounts for the lack of FSH mitogenic effect in prepubertal rat Sertoli cells

Joëlle Dupont , Astrid Musnier , Jérémy Decourtye , Thomas Boulo , Charlotte Lécureuil , Hervé Guillou , Sophie Valet , Sophie Fouchécourt , Jean-Luc Pitetti , Serge Nef , Eric Reiter , Pascale Crépieux

Follicle-stimulating hormone (FSH) controls the proliferation and differentiation of Sertoli cells of the testis. FSH binds a G protein-coupled receptor (GPCR) to stimulate downstream effectors of the phosphoinositide-3 kinase (PI3K)-dependent pathway, without enhancing PI3K activity. To clarify this paradox, we explored the activity of phosphatase and tensin homolog deleted in chromosome 10 (PTEN), the PI3K major regulator, in primary cultures of rat Sertoli cells. We show that, within minutes, FSH increases PTEN neosynthesis, requiring the proteasomal degradation of an unidentified intermediate, as well as PTEN enzymatic activity. Importantly, introducing an antisense cDNA of PTEN into differentiating Sertoli cells restores FSH-dependent cell proliferation. In conclusion, these results provide a new mechanism of PTEN regulation, which could serve to block entry into S phase of Sertoli cells, while they are proceeding through differentiation in pre-pubertal animals.

Mots clés: FSH; PTEN; cell differentiation (rat testis); (Sertoli cells)

Joëlle Dupont, Astrid Musnier, Jérémy Decourtye, Thomas Boulo, Charlotte Lécureuil, et al.. FSH-stimulated PTEN activity accounts for the lack of FSH mitogenic effect in prepubertal rat Sertoli cells. Molecular and Cellular Endocrinology, 2009, 315 (1-2), pp.271. ⟨10.1016/j.mce.2009.09.016⟩. ⟨hal-00547657⟩