FSH-stimulated PTEN activity accounts for the lack of FSH mitogenic effect in prepubertal rat Sertoli cells.
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 neo-synthesis, 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 prepubertal animals.
Dupont
Joëlle
J
BIOS group, INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
Musnier
Astrid
A
Decourtye
Jérémy
J
Boulo
Thomas
T
Lécureuil
Charlotte
C
Guillou
Hervé
H
Valet
Sophie
S
Fouchécourt
Sophie
S
Pitetti
Jean-Luc
JL
Nef
Serge
S
Reiter
Eric
E
Crépieux
Pascale
P
D000818:Animals; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011627:Puberty / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013552:Swine; D014168:Transferrin / Q000378:metabolism
D010716:Phosphatidylinositols; D014168:Transferrin; D005640:Follicle Stimulating Hormone; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat