scholarly journals Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 791-799 ◽  
Author(s):  
Lisa M Mehlmann
Keyword(s):  
G Protein ◽  
Oocyte Maturation ◽  
Cumulus Cells ◽  
Follicle Cells ◽  
Meiotic Maturation ◽  
Meiotic Arrest ◽  
Epidermal Growth ◽  
High Level ◽  
G Protein Coupled ◽  
Stimulation Of

Mammalian oocytes grow and undergo meiosis within ovarian follicles. Oocytes are arrested at the first meiotic prophase, held in meiotic arrest by the surrounding follicle cells until a surge of LH from the pituitary stimulates the immature oocyte to resume meiosis. Meiotic arrest depends on a high level of cAMP within the oocyte. This cAMP is generated by the oocyte, through the stimulation of the GsG-protein by the G-protein-coupled receptor, GPR3. Stimulation of meiotic maturation by LH occurs via its action on the surrounding somatic cells rather than on the oocyte itself. LH induces the expression of epidermal growth factor-like proteins in the mural granulosa cells that act on the cumulus cells to trigger oocyte maturation. The signaling pathway between the cumulus cells and the oocyte, however, remains unknown. This review focuses on recent studies highlighting the importance of the oocyte in producing cAMP to maintain arrest, and discusses possible targets at the level of the oocyte on which LH could act to stimulate meiotic resumption.

scholarly journals Oocyte maturation in starfish is mediated by the beta gamma-subunit complex of a G-protein.

1993 ◽  
Vol 121 (4) ◽  
pp. 775-783 ◽  
Author(s):  
L A Jaffe ◽  
C J Gallo ◽  
R H Lee ◽  
Y K Ho ◽  
T L Jones
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Oocyte Maturation ◽  
Alpha Subunit ◽  
Meiotic Maturation ◽  
Amino Terminus ◽  
Hormone Response ◽  
Gamma Subunit ◽  
Gamma Subunits ◽  
Stimulation Of

The stimulation of meiotic maturation of starfish oocytes by the hormone 1-methyladenine is mimicked by injection of beta gamma subunits of G-proteins from either retina or brain. Conversely, the hormone response is inhibited by injection of the GDP-bound forms of alpha i1 or alpha t subunits, or by injection of phosducin; all of these proteins should bind free beta gamma. alpha-subunit forms with reduced affinity for beta gamma (alpha i1 or alpha t bound to hydrolysis-resistant GTP analogs, or alpha i1-GMPPCP treated with trypsin to remove the amino terminus of the protein) are less effective inhibitors of 1-methyladenine action. These results indicate that the beta gamma subunit of a G-protein mediates 1-methyladenine stimulation of oocyte maturation.

DISSOCIATION BETWEEN LH-INDUCED AEROBIC GLYCOLYSIS AND OOCYTE MATURATION IN CULTURED GRAAFIAN FOLLICLES OF THE RAT

1976 ◽  
Vol 81 (2) ◽  
pp. 362-366 ◽  
Author(s):  
A. Tsafriri ◽  
M. E. Lieberman ◽  
K. Ahrén ◽  
H. R. Lindner
Keyword(s):  
Energy Source ◽  
Luteinizing Hormone ◽  
Oocyte Maturation ◽  
Aerobic Glycolysis ◽  
Follicle Cells ◽  
Meiotic Arrest ◽  
Lactate Accumulation ◽  
Glycolytic Activity ◽  
Stimulation Of

ABSTRACT Luteinizing hormone (NIH-LH-S18; 5 μg/ml) stimulated aerobic glycolysis in cultured Graafian follicles explanted from pro-oestrous rats before the preovulatory gonadotrophin surge: lactate accumulation in the medium was 70 % above control levels during 6 h incubations. Iodoacetate (2.5× 10-5 m) prevented this effect, without impairing the ability of LH to induce resumption of oocytic meiosis. Enrichment of the medium with pyruvate (3.3 × 10-4 m) or lactate (2.5 × 10-2 m) did not in itself cause ovum maturation. The results do not support the hypothesis that termination of meiotic arrest by LH is due to stimulation of glycolytic activity in the follicle cells, resulting in increased availability of an energy source readily utilizable by the oocyte.

Mechanisms of Estradiol-induced EGF-like Factor Expression and Oocyte Maturation via G Protein-coupled Estrogen Receptor

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Hui Zhang ◽  
Sihai Lu ◽  
Rui Xu ◽  
Yaju Tang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Oocyte Maturation ◽  
Polar Body ◽  
Cumulus Cells ◽  
Mitochondrial Activity ◽  
Creb Phosphorylation ◽  
First Polar Body ◽  
Factor Expression ◽  
G Protein Coupled

Abstract Estrogen is an important modulator of reproductive activity through nuclear receptors and G protein–coupled estrogen receptor (GPER). Here, we observed that both estradiol and the GPER-specific agonist G1 rapidly induced cyclic adenosine monophosphate (cAMP) production in cumulus cells, leading to transient stimulation of phosphorylated cAMP response element binding protein (CREB), which was conducive to the transcription of epidermal growth factor (EGF)-like factors, amphiregulin, epiregulin, and betacellulin. Inhibition of GPER by G15 significantly reduced estradiol-induced CREB phosphorylation and EGF-like factor gene expression. Consistently, the silencing of GPER expression in cultured cumulus cells abrogated the estradiol-induced CREB phosphorylation and EGF-like factor transcription. In addition, the increase in EGF-like factor expression in the cumulus cells is associated with EGF receptor (EFGR) tyrosine kinase phosphorylation and extracellular signal–regulated kinase 1/2 (ERK1/2) activation. Furthermore, we demonstrated that GPER-mediated phosphorylation of EGFR and ERK1/2 was involved in reduced gap junction communication, cumulus expansion, increased oocyte mitochondrial activity and first polar body extrusion. Overall, our study identified a novel function for estrogen in regulating EGFR activation via GPER in cumulus cells during oocyte maturation.

scholarly journals The Xenopus laevis Isoform of G Protein-Coupled Receptor 3 (GPR3) Is a Constitutively Active Cell Surface Receptor that Participates in Maintaining Meiotic Arrest in X. laevis Oocytes

2008 ◽  
Vol 22 (8) ◽  
pp. 1853-1865 ◽  
Author(s):  
James Deng ◽  
Stephanie Lang ◽  
Christopher Wylie ◽  
Stephen R. Hammes
Keyword(s):  
Cell Surface ◽  
Xenopus Laevis ◽  
G Protein ◽  
Oocyte Maturation ◽  
Cell Surface Receptor ◽  
Xenopus Laevis Oocytes ◽  
Intracellular Camp ◽  
G Protein Coupled Receptor ◽  
Meiotic Arrest ◽  
G Protein Coupled

Abstract Oocytes are held in meiotic arrest in prophase I until ovulation, when gonadotropins trigger a subpopulation of oocytes to resume meiosis in a process termed “maturation.” Meiotic arrest is maintained through a mechanism whereby constitutive cAMP production exceeds phosphodiesterase-mediated degradation, leading to elevated intracellular cAMP. Studies have implicated a constitutively activated Gαs-coupled receptor, G protein-coupled receptor 3 (GPR3), as one of the molecules responsible for maintaining meiotic arrest in mouse oocytes. Here we characterized the signaling and functional properties of GPR3 using the more amenable model system of Xenopus laevis oocytes. We cloned the X. laevis isoform of GPR3 (XGPR3) from oocytes and showed that overexpressed XGPR3 elevated intraoocyte cAMP, in large part via Gβγ signaling. Overexpressed XGPR3 suppressed steroid-triggered kinase activation and maturation of isolated oocytes, as well as gonadotropin-induced maturation of follicle-enclosed oocytes. In contrast, depletion of XGPR3 using antisense oligodeoxynucleotides reduced intracellular cAMP levels and enhanced steroid- and gonadotropin-mediated oocyte maturation. Interestingly, collagenase treatment of Xenopus oocytes cleaved and inactivated cell surface XGPR3, which enhanced steroid-triggered oocyte maturation and activation of MAPK. In addition, human chorionic gonadotropin-treatment of follicle-enclosed oocytes triggered metalloproteinase-mediated cleavage of XGPR3 at the oocyte cell surface. Together, these results suggest that GPR3 moderates the oocyte response to maturation-promoting signals, and that gonadotropin-mediated activation of metalloproteinases may play a partial role in sensitizing oocytes for maturation by inactivating constitutive GPR3 signaling.

scholarly journals Epidermal Growth Factor Family Members: Endogenous Mediators of the Ovulatory Response

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 77-84 ◽  
Author(s):  
H. Ashkenazi ◽  
X. Cao ◽  
S. Motola ◽  
M. Popliker ◽  
M. Conti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Oocyte Maturation ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Meiotic Maturation ◽  
Expression Of Genes ◽  
Epidermal Growth ◽  
Stimulation Of

Previous studies showed that epidermal growth factor (EGF) and TGFα mimic the action of LH on the resumption of oocyte maturation. We tested whether EGF-like agents, such as amphiregulin (AR), epiregulin (ER), and betacellulin (BTC), also mediate the LH stimulation of the ovulatory response in the rat. LH induced transient follicular expression of AR, ER, and BTC mRNA, reaching a maximum after 3-h incubation. Furthermore, the addition of ER, AR, and BTC to the culture medium could mimic some of LH actions. AR and ER fully simulated LH-induced resumption of meiosis in vitro, whereas BTC was less effective. To study the putative involvement of EGF-like factors in mediation of LH signal, the effect of the EGF receptor kinase inhibitor AG1478 was tested. When added with LH, AG1478, but not its inactive analog AG43, reduced EGF receptor phosphorylation and oocyte maturation compared with follicles treated with LH only. In addition to the inhibition of resumption of meiosis, AG1478 administration into the bursa (3 μg/bursa) resulted in 51% (P < 0.0005) inhibition of ovulation in the treated ovaries, compared with the untreated contralateral ones, as well as to the vehicle-treated ovaries (P < 0.02). LH, as well as ER, induced the expression of genes associated with the ovulatory response like rat hyaluronan synthase-2, cycloxygenase-2, and TNFα-stimulated gene 6 mRNA, whereas AG1478 inhibited this effect of LH. Release of EGF-like factors from the membrane is dependent on activated metalloproteases. Indeed, Galardin, a broad-spectrum metalloprotease inhibitor, but not a specific matrix metalloprotease 2 and 9 inhibitor, suppressed meiotic maturation induced by LH. Conversely, meiotic maturation induced by ER was not affected by Galardin, thus, supporting the notion that LH releases follicular membrane-bound EGF-like agents. In summary, EGF-like factors such as ER, AR, and BTC seem to mediate, at least partially, the LH stimulation of oocyte maturation, ovulatory enzyme expression, and ovulation.

scholarly journals Estrogen Action Via the G Protein-Coupled Receptor, GPR30: Stimulation of Adenylyl Cyclase and cAMP-Mediated Attenuation of the Epidermal Growth Factor Receptor-to-MAPK Signaling Axis

2002 ◽  
Vol 16 (1) ◽  
pp. 70-84 ◽  
Author(s):  
Edward J. Filardo ◽  
Jeffrey A. Quinn ◽  
A. Raymond Frackelton ◽  
Kirby I. Bland
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Egf Receptor ◽  
G Protein Coupled Receptor ◽  
Estrogen Action ◽  
Epidermal Growth ◽  
G Protein Coupled ◽  
Stimulation Of

Abstract Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gβγ-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17β-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERβ, but not ERα, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Gαs subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17α-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.

Sustained muscle contraction induced by agonists, growth factors, and Ca2+ mediated by distinct PKC isozymes

2000 ◽  
Vol 279 (1) ◽  
pp. G201-G210 ◽  
Author(s):  
K. S. Murthy ◽  
J. R. Grider ◽  
J. F. Kuemmerle ◽  
G. M. Makhlouf
Keyword(s):  
Growth Factors ◽  
G Protein ◽  
Muscle Cells ◽  
Sustained Contraction ◽  
Calphostin C ◽  
Epidermal Growth ◽  
Pkc Isozymes ◽  
G Protein Coupled ◽  
Pkc Activation

The role of protein kinase C (PKC) in sustained contraction was examined in intestinal circular and longitudinal muscle cells. Initial contraction induced by agonists (CCK-8 and neuromedin C) was abolished by 1) inhibitors of Ca2+ mobilization (neomycin and dimethyleicosadienoic acid), 2) calmidazolium, and 3) myosin light chain (MLC) kinase (MLCK) inhibitor KT-5926. In contrast, sustained contraction was not affected by these inhibitors but was abolished by 1) the PKC inhibitors chelerythrine and calphostin C, 2) PKC-ε antibody, and 3) a pseudosubstrate PKC-ε inhibitor. GDPβS abolished both initial and sustained contraction, whereas a Gαq/11 antibody inhibited only initial contraction, implying that sustained contraction was dependent on activation of a distinct G protein. Sustained contraction induced by epidermal growth factor was inhibited by calphostin C, PKC-α,β,γ antibody, and a pseudosubstrate PKC-α inhibitor. Ca2+ (0.4 μM) induced an initial contraction in permeabilized muscle cells that was blocked by calmodulin and MLCK inhibitors and a sustained contraction that was blocked by calphostin C and a PKC-α,β,γ antibody. Thus initial contraction induced by Ca2+, agonists, and growth factors is mediated by MLCK, whereas sustained contraction is mediated by specific Ca2+-dependent and -independent PKC isozymes. G protein-coupled receptors are linked to PKC activation via distinct G proteins.

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