Involvement of epidermal growth factor receptor (EGFR) signaling in estrogen inhibition of oocyte maturation mediated through G protein-coupled estrogen receptor 1 (GPER) in zebrafish (Danio rerio)

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Title: Involvement of epidermal growth factor receptor (EGFR) signaling in estrogen inhibition of oocyte maturation mediated through G protein-coupled estrogen receptor 1 (GPER) in zebrafish (Danio rerio)
Author: Peyton, Candace Ann
Abstract: Oocyte maturation (OM ) in teleosts is under precise hormonal control by estrogens and progestins . We show here that estrogens activate an epidermal growth factor receptor (EGFR ) signaling pathway through the G protein -coupled estrogen receptor (GPER ) to maintain meiotic arrest of full -grown zebrafish (Danio rerio ) oocytes in an in vitro germinal vesicle breakdown (GVBD ) bioassay . A GPER - specific agonist decreased OM and a GPER -specific antagonist increased spontaneous OM , whereas specific nuclear estrogen receptor (ERα and ERβ ) agonists did not affect OM , which suggests the inhibitory action of estrogens on OM are solely mediated through GPER . Furthermore , a peptide -bound estrogen , which cannot enter the oocyte , decreased GVBD , showing that these estrogen actions are mediated through a membrane receptor . Treatment of oocytes with actinomycin D , a transcription inhibitor , did not block the inhibitory effects of estrogens on OM , indicating that estrogens act via a nongenomic mechanism to maintain oocyte meiotic arrest . EGFR mRNA was detected in denuded zebrafish oocytes by reverse transcription polymerase chain reaction (RT -PCR ) . Therefore , the potential role of transactivation of EGFR in estrogen inhibition of OM was investigated . The matrix metalloproteinase inhibitor , ilomastat , which prevents the release of heparin -bound epidermal growth factor (HB -EGF ) , increased spontaneous OM . Moreover , specific EGFR1 (ErbB1 ) inhibitors and inhibitors of extracellular -related kinase 1 and 2 (ERK1 /2 ) increased spontaneous OM . Previously , estrogens have been shown to increase 3’ -5’ -cyclic adenosine mono phosphate (cAMP ) levels through GPER in zebrafish oocytes during meiotic arrest . Taken together these present results suggest that estrogens also act through GPER to maintain meiotic arrest through a second signaling pathway involving transactivation of EGFR and activation of ERK 1 and 2 .
URI: http : / /hdl .handle .net /2152 /ETD -UT -2010 -05 -1083
Date: 2010-10-26

Citation

Involvement of epidermal growth factor receptor (EGFR) signaling in estrogen inhibition of oocyte maturation mediated through G protein-coupled estrogen receptor 1 (GPER) in zebrafish (Danio rerio). Master's thesis, University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /ETD -UT -2010 -05 -1083 .

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