FSH-induced phosphoprotein phosphatase 2A-mediated deactivation of particulate phosphodiesterase-4 activities is abolished after alteration in proteoglycan synthesis in immature rat Sertoli cells

Abstract

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-dayold 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.

Influence of gallic acid on porcine neutrophils phosphodiesterase 4, IL-6, TNF-α and rat arthritis model

“…The cAMP-PDE activity was detected using the method described in our previous report . To identify the cAMP-PDE4 activity, a specific inhibitor, rolipram, was added to the incubation mixture at a final concentration of 10 µmol L -1 (Levallet et al 2008). The PDE activity measured in the presence of rolipram was subtracted from the total activity to quantify the PDE4 activity.…”

A Biphasic and Brain-Region Selective Down-Regulation of Cyclic Adenosine Monophosphate Concentrations Supports Object Recognition in the Rat

“…Finally, early increases in cAMP levels followed by an immediate drop in cAMP concentrations have already been well described in cell differentiation, particularly in Sertoli cells [58]. Indeed, before the cAMP increase, stimulation of Sertoli cells by gonadotropin leads to an activation of the ERK pathway, while following the peak of cAMP, gonadotropin activates the PKA pathway.…”

“…Effects induced by 5-HT4R stimulation are time-limited since PKA phosphorylation of 5-HT4R, GRK2 or PDE can be reversed by phosphatase (PP) activity [58]. PP1 and PP2, compartmentalized inside the mammalian cell [93], [94], account for the major phosphatase activities [56]; PP2 is however more particularly investigated because of its ability to dephosphorylate many signaling proteins [93].…”

“…Following the different treatments and at the end of the testing trial, we also examined in these brain sub-regions i) the PDE activities to validate efficiency of PDE3 or PDE4 inhibition by their respective inhibitor and ii) the phosphoprotein phosphatase (PP) type 2 activities since cAMP concentrations have been shown to be transiently up- or down-regulated by PP2A activation in various cell types [53]–[55]. In fact, as cAMP-PDE limit excessive cAMP production by catalysing its hydrolysis; PP1 and PP2 (accounting for more than 90% of total phosphatase activity in brain [56]) limit PDE-induced excessive catabolism of cAMP by reversing PP2A phosphorylation of phosphorylated PPE3B [57] or particulate PDE4 activities [58]. We also demonstrate here, that milrinone alters type PP2 activities in anatomical structures linked to object recognition memory in rat.…”

Molecular crosstalk between insulin‐like growth factors and follicle‐stimulating hormone in the regulation of granulosa cell function

“… 206 , 207 , 208 , 209 Accordingly, it has been shown that PP2A activity is stimulated by FSH and PKA. 210 , 211 Thus, FSH may contribute to PP1 and PP2A activation, which in turn dephosphorylate inhibitory serine residues on IRS2 or IGF1R stimulating their activity (Figure 6 ).…”