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Weiner Sander

Member since: 3rd Jun 2018
Bio: Because the volume of the cumulus-oocyte complex is only a few percent of the total follicle volume, any phosphodiesterase activity increase in the cumulus cells or oocyte would not be detected by measuring activity in lysates of whole follicles. Likewise, the cGMP decrease occurs in the mural granulosa cells but not in the theca cells 4 With a delay, the cGMP decrease also occurs in the cumulus cells and oocyte that are connected to the mural granulosa cells by gap junctions, but our measurements do not provide information as to whether cGMP PDE activity increases in these compartments. Thus, LH signaling reduces cGMP in the follicle by at least two complementary mechanisms: activation of cGMP hydrolysis by PDE5 and inhibition of cGMP synthesis by NPR2 ( Fig. We have previously shown that LH signaling reduces the activity of the NPR2 guanylyl cyclase, which accounts for part of the decline in cGMP in both rat and mouse follicles 18 , 19 Here, we show that LH signaling increases the phosphorylation of PDE5 at serine 92 as well as its cGMP-hydrolytic activity. 6A ). None of these phosphodiesterase inhibitor treatments prevented NEBD in response to isolating the oocyte from the follicle ( Fig. PDE5 and PDE1 inhibitors synergistically inhibit NEBD in response to LH treatment of follicles. As mentioned above, 100 nM Fildena inhibits both PDE5 and PDE6, but because little or no PDE6 protein was detected in rat follicles ( Supplemental Fig. Preovulatory follicles were pre-incubated for 1 h with 100 nM Fildena, 3 μM PF-04822163 (PDE1 inhibitor), or both inhibitors in combination ( Fig. To investigate if PDE5 and PDE1 activities are required for LH-induced meiotic resumption, we examined the effects of PDE5 and PDE1 inhibitors on NEBD, which marks the prophase-to-metaphase transition. S7 ). In summary, our results obtained using forskolin and H89, as well as the presence of a consensus protein kinase A/G site in PDE5 at serine 92 and the evidence discussed above arguing against regulation by way of protein kinase G or the EGFR kinase, all support the hypothesis that increased protein kinase A activity is responsible for the LH-induced increases in PDE5 activity and phosphorylation. Rat follicles treated with the adenylyl cyclase activator forskolin (100 μM, 30 min) had increased PDE5 activity, comparable to that seen in response to LH ( Fig. Evidence that protein kinase A is responsible for the LH-induced increases in PDE5 activity and phosphorylation. Evidence that Protein Kinase A Is Responsible for the LH-induced Increases in PDE5 Phosphorylation and Activity.

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