Cyclic GMP phosphodiesterase and guanylate cyclase activities in rabbit ovaries and the effect of in-vivo stimulation with LH

Patwardhan, Vasant V.; Lanthier, André

doi:10.1677/joe.0.1010305

Cited by 15 publications

(16 citation statements)

References 11 publications

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“…The decrease in cGMP in the follicle does not appear to be associated with follicular activation of cGMP-PDEs, as we were unable to detect increased activity of these enzymes over a period of 2 h of LH stimulation (data not shown), consistent with a previous study [42] in the rabbit. Results of another study [43] have shown that gonadotropins do not affect cGMP hydrolysis in cultured granulosa cells.…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, LH still causes a decrease in cGMP in the presence of PDE5 inhibitors, further excluding the possibility that LH acts through activation of a cGMP-PDE. In several species, LH modulates NO production [23,44,45], which may in turn modulate guanylate cyclase activity [42]. Therefore, it is possible that the mechanism by which LH regulates cGMP in the mouse POF is via the NO-guanylate cyclase pathway.…”

Section: Discussionmentioning

confidence: 99%

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Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes1

Vaccari

Weeks

Hsieh

et al. 2009

Biology of Reproduction

271

276

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It is well established that cAMP signaling is an important regulator of the oocyte meiotic cell cycle. Conversely, the function of cGMP during oocyte maturation is less clear. Herein, we evaluated the expression of cGMP-hydrolyzing phosphodiesterases (PDEs) in the somatic and germ cell compartments of the mouse ovarian follicle and demonstrate that PDE5 is preferentially expressed in somatic cells. Cyclic GMP is a potent inhibitor of cAMP hydrolysis from oocyte extracts, with a 50% inhibitory concentration of 97 nM. Luteinizing hormone (LH) stimulation of cultured preovulatory follicles results in a marked decrease in cGMP content, and a nadir is reached in 1.5 h; similarly, oocyte cGMP levels decrease after gonadotropin stimulation in vivo. The LH-dependent decrease in cGMP requires activation of the epidermal growth factor network. Treatment of follicles with a PDE5 inhibitor increases cGMP in the follicle well above unstimulated levels. Although LH causes a decrease in cGMP in follicles preincubated with PDE5 inhibitors, the levels of this nucleotide remain above unstimulated levels. Under these conditions of elevated cGMP, LH stimulation does not cause oocyte maturation after 5 h of incubation. Microinjection of a cGMP-specific PDE into oocytes causes meiotic maturation of wild-type oocytes, suggesting that an intraoocyte pool of cGMP is involved in the maintenance of meiotic arrest. This effect is absent in PDE3A-deficient oocytes. Taken together, these findings provide evidence that cGMP and cAMP signaling cooperate in maintaining meiotic arrest via regulation of PDE3A and that a decrease in cGMP in the somatic compartment is one of the signals contributing to meiotic maturation.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes1

Vaccari

Weeks

Hsieh

et al. 2009

Biology of Reproduction

271

276

View full text Add to dashboard Cite

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“…The decrease in cGMP in the somatic cells could result from inhibition of a guanylyl cyclase or from stimulation of a cGMP phosphodiesterase. There is some evidence for regulation of the cyclase rather than the phosphodiesterase (Patwardhan and Lanthier, 1984), although it remains to be determined which particular guanylyl cyclases and/or phosphodiesterases are involved, how they are regulated, and whether interfering with LH-induced changes in their activity prevents meiotic resumption. It is also unknown whether EGF receptor activation functions in the pathway by which LH causes cGMP levels to decrease in the somatic cells.…”

Section: Monitoring Camp and Cgmp Levels In Intact Follicle-enclosed mentioning

confidence: 99%

Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte

et al. 2009

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Mammalian oocytes are arrested in meiotic prophase by an inhibitory signal from the surrounding somatic cells in the ovarian follicle. In response to luteinizing hormone (LH), which binds to receptors on the somatic cells, the oocyte proceeds to second metaphase, where it can be fertilized. Here we investigate how the somatic cells regulate the prophase-to-metaphase transition in the oocyte, and show that the inhibitory signal from the somatic cells is cGMP. Using FRET-based cyclic nucleotide sensors in follicleenclosed mouse oocytes, we find that cGMP passes through gap junctions into the oocyte, where it inhibits the hydrolysis of cAMP by the phosphodiesterase PDE3A. This inhibition maintains a high concentration of cAMP and thus blocks meiotic progression. LH reverses the inhibitory signal by lowering cGMP levels in the somatic cells (from ~2 μM to ~80 nM at 1 hour after LH stimulation) and by closing gap junctions between the somatic cells. The resulting decrease in oocyte cGMP (from ~1 μM to ~40 nM) relieves the inhibition of PDE3A, increasing its activity by ~5-fold. This causes a decrease in oocyte cAMP (from ~700 nM to ~140 nM), leading to the resumption of meiosis.

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“…The increased activity of cGMP-PDEs is unable to be detected during LH stimulation [19,101], and gonadotropins do not affect cGMP hydrolysis in cultured granulosa cells [102]. Furthermore, LH still causes a decrease in cGMP in the presence of cGMP special PDE5 inhibitors [19].…”

Section: Lh-induced Meiotic Resumptionmentioning

confidence: 99%

“…These results exclude the possibility that LH acts through activation of a cGMP-PDE. There is some evidence for regulation of the cyclase rather than the phosphodiesterase [101]. It is interesting that Nppc and Npr2 mRNA levels, and NPPC peptide levels are decreased in mouse follicle cells and human follicular fluid after treated by human chorionic gonadotropin (hCG), a pregnancy hormone that exhibits LH activity with a long serum half-life ( [71,103], and data not shown), which could decrease cGMP levels in the follicle cells.…”

Section: Lh-induced Meiotic Resumptionmentioning

confidence: 99%

Hormonal control of mammalian oocyte meiosis at diplotene stage

Zhang

Xia

2011

Cell. Mol. Life Sci.

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Mammalian oocytes grow and undergo meiosis within ovarian follicles. Fully grown oocytes are arrested at the first meiotic prophase by a mural granulosa origin "arrester" until a surge of luteinizing hormone (LH) from the pituitary at the mid-cycle stimulates the immature oocyte to resume meiosis. Recent evidence indicates that natriuretic peptide precursor type C (NPPC) produced by mural granulosa cells stimulates the generation of cyclic guanosine 3',5'-monophosphate (cGMP) by cumulus cell natriuretic peptide receptor 2 (NPR2), which diffuses into oocyte via gap junctions and inhibits oocyte phosphodiesterase 3A (PDE3A) activity and cyclic adenosine 3',5'-monophosphate (cAMP) hydrolysis and maintains meiotic arrest with a high intraoocyte cAMP level. This cAMP is generated through the activity of the Gs G-protein by the G-protein-coupled receptor, GPR3 and GPR12, and adenylyl cyclases (ADCY) endogenous to the oocyte. Further studies suggest that endocrine hormones, such as follicle-stimulating hormone (FSH), LH, 17β-estradiol (E2) and oocyte-derived paracrine factors (ODPFs), participate in oocyte meiosis possibly by the regulation of NPPC and/or NPR2. A detailed investigation of NPPC and NPR2 expression in follicle cells will elucidate the precise molecular mechanisms of gonadotropins, and control the arrest as well as resumption of meiosis.

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Cyclic GMP phosphodiesterase and guanylate cyclase activities in rabbit ovaries and the effect of in-vivo stimulation with LH

Cited by 15 publications

References 11 publications

Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes1

Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes1

Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte

Hormonal control of mammalian oocyte meiosis at diplotene stage

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