PUBLICATION

Involvement of Epidermal Growth Factor Receptor Signaling in Estrogen Inhibition of Oocyte Maturation Mediated Through the G Protein-Coupled Estrogen Receptor (Gper) in Zebrafish (Danio rerio)

Authors
Peyton, C., and Thomas, P.
ID
ZDB-PUB-110316-34
Date
2011
Source
Biology of reproduction   85(1): 42-50 (Journal)
Registered Authors
Keywords
Estradiol/Estradiol receptor, Meiosis, EGFR, GPER, GPR30
MeSH Terms
  • Receptors, G-Protein-Coupled/metabolism*
  • Collagenases
  • Female
  • Estrogens/metabolism
  • Oocytes/growth & development*
  • MAP Kinase Signaling System
  • GTP-Binding Protein gamma Subunits/metabolism*
  • GTP-Binding Protein beta Subunits/metabolism*
  • Transcriptional Activation
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Animals
  • Zebrafish
  • Zebrafish Proteins/metabolism*
(all 13)
PubMed
21349822 Full text @ Biol. Reprod.
Abstract
Oocyte maturation (OM) in teleosts is under precise hormonal control by progestins and estrogens. We show here that estrogens activate an epidermal growth factor receptor (Egfr) signaling pathway in full-grown denuded zebrafish oocytes through the G protein coupled estrogen receptor, Gper (or GPR30), to maintain oocyte meiotic arrest in a germinal vesicle breakdown (GVBD) bioassay. A GPER-specific antagonist, G-15, increased spontaneous OM, indicating that the inhibitory estrogen actions on OM are mediated through Gper. Estradiol-17beta-bovine serum albumen (BSA), which cannot enter oocytes, decreased GVBD, whereas treatment with Actinomycin D did not block estrogen's inhibitory effects, suggesting that estrogens act at the cell surface via a nongenomic mechanism to prevent OM. The intracellular tyrosine kinase (Src) inhibitor, PP2, blocked estrogen inhibition of OM. Expression of egfr mRNA and Egfr protein were detected in denuded zebrafish oocytes. The matrix metalloproteinase (MMP) inhibitor, ilomastat, which prevents the release of heparin-bound epidermal growth factor (HB-EGF), increased spontaneous OM, while the MMP activator, interleukin-1alpha, decreased spontaneous OM. Moreover, inhibitors of EGFR (ErbB1) and extracellular-related kinase 1 and 2 (Erk1/2, official symbol Mapk3/1) increased spontaneous OM. In addition, E2 and G-1 increased phosphorylation of Erk, and this was abrogated by simultaneous treatment with the EGFR inhibitor. Taken together these results suggest that estrogens act through Gper to maintain meiotic arrest via a Src kinase-dependent G-protein betagamma subunit signaling pathway involving transactivation of egfr and phosphorylation of Mapk3/1. This is the first evidence that epidermal growth factor receptor signaling in vertebrate oocytes can prevent meiotic progression.
Genes / Markers
Figures
No images available
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Peyton, C., and Thomas, P. (2011) Involvement of Epidermal Growth Factor Receptor Signaling in Estrogen Inhibition of Oocyte Maturation Mediated Through the G Protein-Coupled Estrogen Receptor (Gper) in Zebrafish (Danio rerio). Biology of reproduction. 85(1):42-50.