Cyclic AMP changes in the component cells of Graafian follicles: Possible influences on maturation in the follicle-enclosed oocytes of hamsters

Hubbard, Christopher

doi:10.1016/0012-1606(86)90003-5

Cited by 35 publications

(18 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A decrease in cGMP concentration, to 40% of the initial value, was previously reported in hamster follicles exposed to LH (Hubbard, 1986).…”

Section: Lh Decreases Cgmp In the Somatic Cells Of The Folliclesupporting

confidence: 71%

“…Thus, it is unknown whether the decreases in cAMP that were observed in response to LH receptor stimulation were sufficient to affect the activity of PKA, which requires cAMP in the range of 70-500 nM for half-maximal activity (Dostmann and Taylor, 1991;Viste et al, 2005). LHstimulated decreases in cGMP occur in oocytes and whole follicles from hamsters (Hubbard, 1986), but whether the magnitude of these changes is physiologically significant and whether these decreases occur in other species are unknown. These are crucial issues because, as noted above, cGMP is not the only regulator of PDE3A; in addition, it is controversial whether relief of inhibitory signals from the somatic cells is the primary mode of LH action (see Eppig et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…A decrease in cGMP concentration, to 40% of the initial value, was previously reported in hamster follicles exposed to LH (Hubbard, 1986).…”

Section: Lh Decreases Cgmp In the Somatic Cells Of The Folliclesupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…How is the rapid loss of oocyte cAMP achieved? LH administration leads to a fall in follicular cGMP (Hubbard 1986) and a loss of gap junctions (SelaAbramovich et al 2005). The involvement of cGMP in the process of meiotic resumption was recently strengthened by the work of Shuhaibar et al (Shuhaibar et al 2015).…”

Section: Lh-induced Changes In Cyclic Nucleotidesmentioning

confidence: 99%

Oocyte maturation and quality: role of cyclic nucleotides

Gilchrist¹,

Luciano²,

Richani³

et al. 2016

Reproduction

166

117

View full text Add to dashboard Cite

The cyclic nucleotides, cAMP and cGMP, are the key molecules controlling mammalian oocyte meiosis. Their roles in oocyte biology have been at the forefront of oocyte research for decades, and many of the long-standing controversies in relation to the regulation of oocyte meiotic maturation are now resolved. It is now clear that the follicle prevents meiotic resumption through the actions of natriuretic peptides and cGMP -inhibiting the hydrolysis of intra-oocyte cAMP -and that the pre-ovulatory gonadotrophin surge reverses these processes.

show abstract

“…LH signaling reduces gap junction permeability (16, 17), but meiosis can resume without the permeability decrease (17), arguing against gap junction closure as a primary mechanism for transmitting the signal. LH signaling also reduces cGMP in the follicle as a whole (4,5,(18)(19)(20), suggesting that the decrease in oocyte cGMP is a consequence of the fall in cGMP in the large volume around the oocyte, to which it is connected by gap junctions (21).Alternatively, recent work has suggested that the LH signal is transmitted to the oocyte by regulation of the release from the mural granulosa cells of peptides that diffuse through the extracellular space to the cumulus cells. In support of this concept, LH signaling decreases the ovarian content of the NPR2 agonist C-type natriuretic peptide, thus decreasing cGMP in the cumulus-oocyte complex (22); however, levels of this peptide decrease only after the decrease in oocyte cGMP (9,20).…”

mentioning

confidence: 99%

Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles

Shuhaibar

Egbert

Norris

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

136

155

View full text Add to dashboard Cite

Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.cyclic GMP | gap junctions | ovarian follicle | oocyte meiosis | luteinizing hormone M eiosis in mammalian oocytes begins during embryonic development and then arrests in late prophase, for up to 50 y in women and for many months in mice. At the time of ovulation, luteinizing hormone (LH) acts on the granulosa cells of the follicle surrounding the oocyte to release the arrest and restart meiosis in preparation for fertilization (1-3). In the mouse preovulatory follicle, inhibition of meiotic progression is dependent upon the cyclic nucleotide cyclic GMP (cGMP), which diffuses from the granulosa cells into the oocyte through gap junctions that connect all cells of the follicle (4-6). The cGMP is produced by the transmembrane guanylyl cyclase natriuretic peptide receptor 2 (NPR2, also known as guanylyl cyclase B), which is present in all of the granulosa cells, but not in the oocyte (7-11). In the oocyte, cGMP inhibits the degradation of another cyclic nucleotide, cAMP, which depends primarily on the phosphodiesterase PDE3A, an enzyme whose activity is antagonized by cGMP (4, 5). The resulting high level of cAMP, through a series of intermediate steps, inhibits meiotic progression (2, 3, 12).LH signaling is initiated in the outer (mural) layers of granulosa cells; receptors for LH are absent in the oocyte and in the granulosa cells that directly surround it (the cumulus cells) (13-15). Ensuing events cause meiosis to resume by reducing cGMP in the oocyte (4, 5), but how LH receptor activation up to 10 cell layers away lowers oocyt...

show abstract

Cyclic AMP changes in the component cells of Graafian follicles: Possible influences on maturation in the follicle-enclosed oocytes of hamsters

Cited by 35 publications

References 21 publications

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

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

Oocyte maturation and quality: role of cyclic nucleotides

Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles

Contact Info

Product

Resources

About