FSH-induced phosphoprotein phosphatase 2A-mediated deactivation of particulate phosphodiesterase-4 activities is abolished after alteration in proteoglycan synthesis in immature rat Sertoli cells.
Cessation of rat testicular Sertoli cells proliferation around days 15-20 post partum is associated in vitro with the highest rise in rolipram-sensitive cAMP-catabolizing phosphodiesterase-4 activities (PDE4s) triggered by FSH during the early postnatal period. The transient nature of FSH-induced increase in PDE4s suggests concomitant changes in both PKA-mediated activation and subsequent deactivation of these activities. In this study, we demonstrated that the deactivation of FSH-stimulated particulate, but not soluble, PDE4s in cultured Sertoli cells from 20-day-old rats was inhibited by phosphoprotein phosphatase (PP) inhibitors, okadaïc acid, and calyculin A. Moreover, the deactivation of FSH-stimulated particulate PDE4s was timely related with the gonadotropin-induced increase in both particulate PP2A activity and particulate PP2A catalytic subunit immunoreactive expression independently of any transcriptional regulation of that subunit. Both the FSH-induced increase in recruitment/activation of particulate PP2A and the subsequent deactivation of particulate PDE4 were abolished when Sertoli cell proteoglycans (PGs) synthesis was altered by sodium chlorate. Sodium chlorate effect was developmentally regulated as evidenced by its ability to silence particulate PDE4 deactivation only in non-proliferating (from 20- to 30-day-old rats) but not in proliferating (from 10-day-old rats) Sertoli cells. All these data suggested that PGs could be involved in the FSH-induced recruitment/activation of PP2A. Particularly, developmentally regulated transmembrane syndecans, the most abundant PGs in Sertoli cells, by targeting PP2A at the membrane level could allow developmental control of activated particulate PDE4s and, potentially, other signaling phosphoproteins, including the FSH receptor, during the early postnatal period.
Levallet
Guénaëlle
G
Laboratoire Estrogènes et Reproduction, UPRES-EA 2608, INRA USC 2006, Université de Caen, 14032 Caen Cedex, France.
Levallet
Jérôme
J
Bonnamy
Pierre-Jacques
PJ
D000818:Animals; D002478:Cells, Cultured; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D008297:Male; D054648:Protein Phosphatase 2 / Q000502:physiology*; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000378:metabolism*; D020358:Sodium Cholate / Q000494:pharmacology
D011509:Proteoglycans; D005640:Follicle Stimulating Hormone; C514014:Ppp2ca protein, rat; D054648:Protein Phosphatase 2; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020358:Sodium Cholate