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Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr.
J Endocrinol. 2015 Apr; 225(1):59-68.JE

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 has been recently obtained using 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 (Gper1) and involves activation of Egfr. Therefore, in this study, the potential roles of Pgrmc1 in the cell surface expression and functions of Egfr in normal cells were investigated in this in vitro OM model of Egfr action using an inhibitor of PGMRC1 signaling, AG205. A single ∼60 kDa 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 (20 μM) 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 (50 μM) 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 indicate 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.

Authors+Show Affiliations

Marine Science InstituteThe University of Texas at Austin, 750 Channel View Drive, Port Aransas, Texas 78373, USA.Marine Science InstituteThe University of Texas at Austin, 750 Channel View Drive, Port Aransas, Texas 78373, USA peter.thomas@utexas.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

25720537

Citation

Aizen, Joseph, and Peter Thomas. "Role of Pgrmc1 in Estrogen Maintenance of Meiotic Arrest in Zebrafish Oocytes Through Gper/Egfr." The Journal of Endocrinology, vol. 225, no. 1, 2015, pp. 59-68.
Aizen J, Thomas P. Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr. J Endocrinol. 2015;225(1):59-68.
Aizen, J., & 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. https://doi.org/10.1530/JOE-14-0576
Aizen J, Thomas P. Role of Pgrmc1 in Estrogen Maintenance of Meiotic Arrest in Zebrafish Oocytes Through Gper/Egfr. J Endocrinol. 2015;225(1):59-68. PubMed PMID: 25720537.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Pgrmc1 in estrogen maintenance of meiotic arrest in zebrafish oocytes through Gper/Egfr. AU - Aizen,Joseph, AU - Thomas,Peter, Y1 - 2015/02/26/ PY - 2015/2/28/entrez PY - 2015/2/28/pubmed PY - 2015/5/27/medline KW - AG205 KW - DHP KW - E2 KW - EGFR KW - GPER KW - PGRMC1 KW - oocyte maturation KW - zebrafish SP - 59 EP - 68 JF - The Journal of endocrinology JO - J. Endocrinol. VL - 225 IS - 1 N2 - 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 has been recently obtained using 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 (Gper1) and involves activation of Egfr. Therefore, in this study, the potential roles of Pgrmc1 in the cell surface expression and functions of Egfr in normal cells were investigated in this in vitro OM model of Egfr action using an inhibitor of PGMRC1 signaling, AG205. A single ∼60 kDa 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 (20 μM) 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 (50 μM) 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 indicate 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. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/25720537/Role_of_Pgrmc1_in_estrogen_maintenance_of_meiotic_arrest_in_zebrafish_oocytes_through_Gper/Egfr_ L2 - https://joe.bioscientifica.com/doi/10.1530/JOE-14-0576 DB - PRIME DP - Unbound Medicine ER -