PUBLICATION
Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr
- Authors
- Aizen, Y., Thomas, P.
- ID
- ZDB-PUB-150301-16
- Date
- 2015
- Source
- The Journal of endocrinology 225(1): 59-68 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Female
- Gene Expression Regulation/physiology
- Meiosis/physiology*
- Oocytes/metabolism*
- Ovary/physiology
- Receptors, Estrogen/genetics
- Receptors, Estrogen/metabolism*
- Receptors, Progesterone/genetics
- Receptors, Progesterone/metabolism*
- Zebrafish
- PubMed
- 25720537 Full text @ J. Endocrinol.
Citation
Aizen, Y., Thomas, P. (2015) Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr. The Journal of endocrinology. 225(1):59-68.
Abstract
The regulation of receptor trafficking to the cell surface and its effect on responses of target cells to growth factors and hormones remain poorly understood. Initial evidence was recently obtained in cancer cells that surface expression of the epidermal growth factor receptor (EGFR) is dependent on its association with progesterone receptor membrane component 1 (PGRMC1). Estrogen inhibition of oocyte maturation (OM) in zebrafish is mediated through G protein-coupled estrogen membrane receptor-1 (Gper), and involves activation of Egfr. Therefore, in the present study the potential role of Pgrmc1 in the cell-surface expression and functions of Egfr in normal cells was investigated in this in vitro OM model of Egfr action using an inhibitor of Pgrmc1 signaling, AG205. A single Pgrmc1 ~ kDa 60 protein band which corresponds to the size of the Pgrmc1 dimer was detected on plasma membranes of fully grown oocytes by Western blotting. Co-treatment with the PGRMC1 inhibitor AG205 (20µM) blocked the inhibitory effects of 100 nM estradiol-17β and the GPER agonist, G-1, on spontaneous maturation of denuded zebrafish oocytes. Moreover, reversal of these estrogen effects on OM by the EGFR inhibitors AG1478 and AG825 (50µM) was prevented by co-incubation with the PGRMC1 inhibitor. Inhibition of Pgrmc1 signaling with AG205 also caused a decrease in Egfr-dependent signaling and Egfr expression on oocyte cell membranes. These results demonstrate that maintenance of Pgrmc1 signaling is required for Egfr expression on zebrafish oocyte cell membranes and for conserving the functions of Egfr in maintaining meiotic arrest through estrogen activation of Gper.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping