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Abstract

Potential regulation of membrane trafficking by estrogen receptor a via induction of Rab11 in uterine glands during implantation (PDF) (HTML) 
Chen,Dahu; Ganapathy,Padmaja; Zhu,Li-Ji; Xu,Xueping; Li,Quanxi; Bagchi,Indrani C.; Bagchi,Milan K.
Molecular Endocrinology 13(6): 993-1004
Publication date: 1999

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The steroid hormone estrogen profoundly influences the earlyevents in the uterus leading to embryo implantation. It is thoughtthat estrogen triggers the expression of a unique set of genes inthe preimplantation endometrium that in turn control implantation. Toidentify these estrogen-induced genes, we used a delayed implantationmodel system in which embryo attachment to endometrium is dependenton estrogen administration. Using a mRNA differential display (DD)method, we isolated a number of cDNAs representing mRNAs whose expressionis either turned on or turned off in response to an implantation-inducingdose of estrogen. We identified one of these cDNAs as that encodingrab11, a p21ras-like GTP-binding protein (G protein), whichfunctions in the targeting of transport vesicles to the plasmamembrane. In normal pregnant rats, rab11 mRNA was expressedat low levels on days 1-2 of pregnancy, but its expressionwas markedly enhanced (6- to 8-fold) between days 3-5immediately before implantation. In situ hybridization and immunocytochemistry revealedthat rab11 expression in the uterus was predominantly in the glandularepithelium. In ovariectomized rats, the expression of rab11 mRNAwas induced in the endometrium in response to estrogen. To determinewhether this effect of estrogen was mediated through its nuclearreceptors, we examined rab11 expression in a transformed endometrialcell line, Ishikawa. In transient transfection experiments, weobserved that overexpression of estrogen receptor (ER) or ß inducedendogenous rab11 mRNA in a hormone-dependent manner. ER bound toan antagonist, ICI 182,780, failed to activate this gene expression. Thesefindings, together with the observation that ER but not ERß isdetected in the glands of the preimplantation uterus, indicatethat rab11 is one of the proteins that are specifically inducedby estrogen-complexed ER in rat endometrium at the onset of implantation.Our results imply that estrogen, which induces the synthesisof many growth factors and their receptors and other secretoryproteins that are thought to be critical for implantation, mayalso facilitate their transport to the membrane and/or secretionby stimulating the expression of rab11, a component of the membrane-traffickingpathway. This study therefore provides novel insights into thediverse cellular mechanisms by which estrogen, acting via itsnuclear receptors, may influence blastocyst implantation.

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