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General Comment |
Conti M, et al 1984 Hormonal regulation of 3',5'-adenosine monophosphate
phosphodiesterases in cultured rat granulosa cells.
The effect of gonadotropins on phosphodiesterase activity of rat granulosa cells was
studied in an in vitro model. Granulosa cells were prepared from hypophysectomized
or intact, estrogen-primed immature female rats and treated with FSH, hCG, or
(Bu)2cAMP in vitro. Phosphodiesterase activity was determined in cell homogenates.
FSH treatment for 2 days produced a marked increase in phosphodiesterase activity,
while hCG was ineffective. FSH stimulation was potentiated by the addition of
1-methyl-3-isobutylxanthine, while treatment with the cAMP analog, (Bu)2cAMP by
itself also markedly stimulated enzyme activity. FSH stimulated cAMP, but not
cGMP, hydrolysis, suggesting that a phosphodiesterase specific for cAMP was
stimulated by the gonadotropin. Time-course studies showed that an increase in
phosphodiesterase activity was apparent after 1 h of incubation and was maximal at
48 h. FSH stimulation of phosphodiesterase was dose-dependent, with an ED50 of 30
ng/ml FSH and a maximal increase at 100-300 ng/ml. Treatment with cycloheximide
(1 or 10 micrograms/ml) completely blocked the gonadotropin stimulation, suggesting
that on-going protein synthesis is required for the FSH action. DEAE-cellulose
chromatography of soluble extracts of control and FSH-treated cells indicated that
two forms of phosphodiesterase were present in unstimulated granulosa cells. The
first form, , likely PDE1, eluting at 0.17 M Na-acetate, hydrolyzed both cAMP and cGMP and was
stimulated by Ca++ and calmodulin; the second form, eluting at 0.48 M Na-acetate,
was insensitive to Ca++ or calmodulin and hydrolyzed mainly cAMP. FSH treatment
markedly stimulated cAMP hydrolysis by the calmodulin-dependent first form as well
as that by the second form.
NCBI Summary:
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE1 subfamily. Members of the PDE1 family are calmodulin-dependent PDEs that are stimulated by a calcium-calmodulin complex. This PDE has dual-specificity for the second messengers, cAMP and cGMP, with a preference for cGMP as a substrate. cAMP and cGMP function as key regulators of many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]
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Comment |
Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis. Egbert JR et al. (2016) The meiotic cell cycle of mammalian oocytes in preovulatory follicles is held in prophase arrest by diffusion of cGMP from the surrounding granulosa cells into the oocyte. Luteinizing hormone (LH) then releases meiotic arrest by lowering cGMP in the granulosa cells. The LH-induced reduction of cGMP is caused in part by a decrease in guanylyl cyclase activity, but the observation that the cGMP phosphodiesterase PDE5 is phosphorylated during LH signaling suggests that an increase in PDE5 activity could also contribute. To investigate this idea, we measured cGMP-hydrolytic activity in rat ovarian follicles. Basal activity was due primarily to PDE1A and PDE5, and LH increased PDE5 activity. The increase in PDE5 activity was accompanied by phosphorylation of PDE5 at serine 92, a protein kinase A/G consensus site. Both the phosphorylation and the increase in activity were promoted by elevating cAMP and opposed by inhibiting protein kinase A, supporting the hypothesis that LH activates PDE5 by stimulating its phosphorylation by protein kinase A. Inhibition of PDE5 activity partially suppressed LH-induced meiotic resumption as indicated by nuclear envelope breakdown, but inhibition of both PDE5 and PDE1 activities was needed to completely inhibit this response. These results show that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism.//////////////////
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