{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:06:35Z","timestamp":1783555595027,"version":"3.55.0"},"reference-count":55,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The steroid hormone estrogen profoundly influences the early events in the uterus leading to embryo implantation. It is thought that estrogen triggers the expression of a unique set of genes in the preimplantation endometrium that in turn control implantation. To identify these estrogen-induced genes, we used a delayed implantation model system in which embryo attachment to endometrium is dependent on estrogen administration. Using a mRNA differential display (DD) method, we isolated a number of cDNAs representing mRNAs whose expression is either turned on or turned off in response to an implantation-inducing dose of estrogen. We identified one of these cDNAs as that encoding rab11, a p21ras-like GTP-binding protein (G protein), which functions in the targeting of transport vesicles to the plasma membrane. In normal pregnant rats, rab11 mRNA was expressed at low levels on days 1\u20132 of pregnancy, but its expression was markedly enhanced (\u223c6- to 8-fold) between days 3\u20135 immediately before implantation. In situ hybridization and immunocytochemistry revealed that rab11 expression in the uterus was predominantly in the glandular epithelium. In ovariectomized rats, the expression of rab11 mRNA was induced in the endometrium in response to estrogen. To determine whether this effect of estrogen was mediated through its nuclear receptors, we examined rab11 expression in a transformed endometrial cell line, Ishikawa. In transient transfection experiments, we observed that overexpression of estrogen receptor (ER) \u03b1 or \u03b2 induced endogenous rab11 mRNA in a hormone-dependent manner. ER bound to an antagonist, ICI 182,780, failed to activate this gene expression. These findings, together with the observation that ER\u03b1 but not ER\u03b2 is detected in the glands of the preimplantation uterus, indicate that rab11 is one of the proteins that are specifically induced by estrogen-complexed ER\u03b1 in rat endometrium at the onset of implantation. Our results imply that estrogen, which induces the synthesis of many growth factors and their receptors and other secretory proteins that are thought to be critical for implantation, may also facilitate their transport to the membrane and\/or secretion by stimulating the expression of rab11, a component of the membrane-trafficking pathway. This study therefore provides novel insights into the diverse cellular mechanisms by which estrogen, acting via its nuclear receptors, may influence blastocyst implantation.<\/jats:p>","DOI":"10.1210\/mend.13.6.0287","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:30:20Z","timestamp":1389202220000},"page":"993-1004","source":"Crossref","is-referenced-by-count":2,"title":["Potential Regulation of Membrane Trafficking by Estrogen Receptor\u03b1 via Induction of Rab11 in Uterine Glands during Implantation"],"prefix":"10.1210","volume":"13","author":[{"given":"Dahu","family":"Chen","sequence":"first","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmaja","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ji","family":"Zhu","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Xu","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanxi","family":"Li","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indrani C.","family":"Bagchi","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan K.","family":"Bagchi","sequence":"additional","affiliation":[{"name":"Population Council and The Rockefeller University New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614190374500_R1","first-page":"187","article-title":"Endocrine control of egg implantation.","author":"Psychoyos","year":"1973","journal-title":"Handbook of Physiology."},{"key":"2020071614190374500_R2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1749-6632.1988.tb22279.x","article-title":"Uterine receptivity for blastocyst implantation.","volume":"541","author":"Yoshinaga","year":"1988","journal-title":"Ann NY Acad Sci"},{"key":"2020071614190374500_R3","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-4684-5589-2_9","article-title":"The Implantation Reaction.","author":"Parr","year":"1989","journal-title":"Biology of The Uterus."},{"key":"2020071614190374500_R4","first-page":"391","article-title":"Biology of implantation.","author":"Weitlauf","year":"1994","journal-title":"The Physiology of Reproduction."},{"key":"2020071614190374500_R5","first-page":"205","article-title":"Hormonal control of ovoimplantation.","volume":"31","author":"Psychoyos","year":"1973","journal-title":"Vitam Horm"},{"key":"2020071614190374500_R6","first-page":"17","article-title":"Hormonal control of uterine receptivity for nidation.","volume":"25","author":"Psychoyos","year":"1976","journal-title":"J Reprod Fertil Suppl"},{"key":"2020071614190374500_R7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1749-6632.1986.tb20920.x","article-title":"Uterine receptivity for nidation.","volume":"476","author":"Psychoyos","year":"1986","journal-title":"Ann NY Acad Sci"},{"key":"2020071614190374500_R8","first-page":"246","article-title":"The implantation reaction","author":"Finn","year":"1971"},{"key":"2020071614190374500_R9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1210\/endo-85-1-103","article-title":"Estrogen secretion by the rat ovary in vivo during the estrous cycle and pregnancy.","volume":"85","author":"Yoshinaga","year":"1969","journal-title":"Endocrinology"},{"key":"2020071614190374500_R10","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1126\/science.3283939","article-title":"The steroid and thyroid hormone receptor superfamily.","volume":"240","author":"Evans","year":"1988","journal-title":"Science"},{"key":"2020071614190374500_R11","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0092-8674(89)90237-7","article-title":"Gene regulation by steroid hormones.","volume":"56","author":"Beato","year":"1989","journal-title":"Cell"},{"key":"2020071614190374500_R12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/mend-4-3-363","article-title":"The steroid receptor superfamily: more excitement predicted for the future.","volume":"4","author":"O\u2019Malley","year":"1990","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R13","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1210\/endo.138.3.5080","article-title":"A new actor in the estrogen receptor drama\u2014enter ER-\u03b2.","volume":"138","author":"Katzenellenbogen","year":"1997","journal-title":"Endocrinology"},{"key":"2020071614190374500_R14","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1210\/endo-120-5-1882","article-title":"Estrogen induction of N-myc and c-myc proto-oncogene expression in the rat uterus.","volume":"120","author":"Murphy","year":"1987","journal-title":"Endocrinology"},{"key":"2020071614190374500_R15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0014-5793(87)81267-X","article-title":"Oestrogen-induced expression of oncogenes in the immature rat uterus.","volume":"211","author":"Travers","year":"1987","journal-title":"FEBS Lett"},{"key":"2020071614190374500_R16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1210\/mend-1-7-445","article-title":"Estrogen induces insulin-like growth factor-1 in the rat uterus.","volume":"1","author":"Murphy","year":"1987","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R17","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1210\/endo-122-6-2355","article-title":"Influence of estrogens on mouse uterine epidermal growth factor precursor protein and messenger ribonucleic acid","volume":"122","author":"DiAugustine","year":"1988","journal-title":"Endocrinology."},{"key":"2020071614190374500_R18","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1210\/mend-2-3-230","article-title":"Estrogen induction of the epidermal growth factor receptor mRNA.","volume":"2","author":"Lingham","year":"1988","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R19","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1210\/mend-2-9-816","article-title":"Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus.","volume":"2","author":"Weisz","year":"1988","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R20","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1210\/mend-2-10-946","article-title":"Estrogen regulation of c-fos messenger ribonucleic acid.","volume":"2","author":"Loose-Mitchell","year":"1988","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R21","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1210\/endo-125-2-597","article-title":"Uterine insulin-like growth factor-1 receptors: regulation by estrogen and variation throughout the estrous cycle.","volume":"125","author":"Ghahary","year":"1989","journal-title":"Endocrinology"},{"key":"2020071614190374500_R22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0960-0760(92)90037-J","article-title":"Estrogen regulates expression of the jun family of protooncogenes in the uterus.","volume":"41","author":"Chiappetta","year":"1992","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071614190374500_R23","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1210\/endo.131.4.1396310","article-title":"Transforming growth factor-\u03b1 is a potential mediator of estrogen action in the mouse uterus.","volume":"131","author":"Nelson","year":"1992","journal-title":"Endocrinology"},{"key":"2020071614190374500_R24","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1210\/endo.133.2.8344219","article-title":"Vascular endothelial growth factor\/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth.","volume":"133","author":"Bove-Cullinan","year":"1993","journal-title":"Endocrinology"},{"key":"2020071614190374500_R25","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1530\/jrf.0.0120593","article-title":"Delayed implantation in the spayed, progesterone treated adult mouse.","volume":"12","author":"Yoshinaga","year":"1966","journal-title":"J Reprod Fertil"},{"key":"2020071614190374500_R26","first-page":"97","article-title":"Endocrine control of implantation and delayed implantation in rats and mice.","volume":"29","author":"Gidley-Baird","year":"1981","journal-title":"J Reprod Fertil [Suppl]"},{"key":"2020071614190374500_R27","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/0955-0674(94)90071-X","article-title":"Rab GT Pases: master regulators of membrane trafficking.","volume":"6","author":"Pfeffer","year":"1994","journal-title":"Curr Opin Cell Biol"},{"key":"2020071614190374500_R28","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/0092-8674(93)90478-9","article-title":"Friends and family: the role of the Rab GTPases in vesicular traffic.","volume":"75","author":"Novick","year":"1993","journal-title":"Cell"},{"key":"2020071614190374500_R29","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.cb.09.110193.003043","article-title":"The role of GTP-binding proteins in transport along the exocytic pathway.","volume":"9","author":"Ferro-Novick","year":"1993","journal-title":"Annu Rev Cell Biol"},{"key":"2020071614190374500_R30","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1126\/science.1354393","article-title":"Differential display of eukaryotic messenger RNA by means of polymerase chain reaction.","volume":"257","author":"Liang","year":"1992","journal-title":"Science"},{"key":"2020071614190374500_R31","doi-asserted-by":"crossref","first-page":"6463","DOI":"10.1073\/pnas.91.14.6463","article-title":"Chronic cardiac rejection: identification of five upregulated genes in transplanted hearts by differential mRNA display.","volume":"91","author":"Utans","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190374500_R32","doi-asserted-by":"crossref","first-page":"6231","DOI":"10.1073\/pnas.91.13.6231","article-title":"Identification of multiple genes in bovine retinal pericytes altered by exposure to elevated levels of glucose by using mRNA differential display.","volume":"91","author":"Aiello","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190374500_R33","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/0006-291X(91)90672-T","article-title":"Molecular cloning and characterization of a ras p21-like GTP-binding protein (24 KG) from rat liver.","volume":"177","author":"Sakurada","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614190374500_R34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0014-5793(98)00607-3","article-title":"Human rab11a: transcription, chromosome mapping and effect on the expression levels of host GTP-binding proteins.","volume":"429","author":"Gromov","year":"1998","journal-title":"FEBS Lett"},{"key":"2020071614190374500_R35","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0010-7824(96)00196-5","article-title":"Anti-implantation activity of antiestrogens and mifepristone.","volume":"54","author":"Dao","year":"1996","journal-title":"Contraception"},{"key":"2020071614190374500_R36","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1210\/endo.138.11.5496","article-title":"Tissue distribution and quantitative analysis of estrogen receptor-\u03b1 (ER\u03b1) and estrogen receptor-\u03b2 (ER\u03b2) messenger ribonucleic acid in the wild-type and ER \u03b1-knockout mouse.","volume":"138","author":"Couse","year":"1997","journal-title":"Endocrinology"},{"key":"2020071614190374500_R37","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1210\/mend-4-3-510","article-title":"Estrogen regulates the synthesis of epidermal growth factor in mouse uterine epithelial cells.","volume":"4","author":"Huet-Hudson","year":"1990","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R38","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1095\/biolreprod46.2.208","article-title":"Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone.","volume":"46","author":"Kapur","year":"1992","journal-title":"Biol Reprod"},{"key":"2020071614190374500_R39","doi-asserted-by":"crossref","first-page":"11408","DOI":"10.1073\/pnas.88.24.11408","article-title":"Uterine expression of leukemia inhibitory factor coincides with the onset of blastocyst implantation.","volume":"88","author":"Bhatt","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190374500_R40","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1210\/endo.135.3.8070372","article-title":"Differential regulation of heparin-binding epidermal growth factor-like growth factor in the adult ovariectomized mouse uterus by progesterone and estrogen.","volume":"135","author":"Wang","year":"1994","journal-title":"Endocrinology"},{"key":"2020071614190374500_R41","doi-asserted-by":"crossref","first-page":"10134","DOI":"10.1016\/S0021-9258(18)61088-9","article-title":"Lactotransferrin is the major estrogen inducible protein of mouse uterine secretions.","volume":"262","author":"Pentecost","year":"1987","journal-title":"J Biol Chem"},{"key":"2020071614190374500_R42","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1210\/endo.130.1.1727726","article-title":"Polarized rat uterine epithelium in vitro: constitutive expression of estrogen-induced proteins.","volume":"130","author":"Julian","year":"1992","journal-title":"Endocrinology"},{"key":"2020071614190374500_R43","first-page":"1441","article-title":"Analysis of transcription and estrogen insensitivity in the female mouse after targeted disruption of the estrogen receptor gene.","volume":"9","author":"Couse","year":"1995","journal-title":"Mol Endocrinol"},{"key":"2020071614190374500_R44","doi-asserted-by":"crossref","first-page":"16941","DOI":"10.1016\/S0021-9258(19)84798-1","article-title":"Estrogen regulation of tissue-specific expression of complement C3.","volume":"264","author":"Sundstrom","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071614190374500_R45","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/mrd.1080390217","article-title":"Leukaemia inhibitory factor and the regulation of pre-implantation development of the mammalian embryo.","volume":"39","author":"Stewart","year":"1994","journal-title":"Mol Reprod Dev"},{"key":"2020071614190374500_R46","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.cb.03.110187.001331","article-title":"Constitutive and regulated secretion of proteins.","volume":"3","author":"Burgess","year":"1987","journal-title":"Annu Rev Cell Biol"},{"key":"2020071614190374500_R47","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/1043-4682(92)90021-M","article-title":"Biogenesis of secretory granules.","volume":"3","author":"Tooze","year":"1992","journal-title":"Semin Cell Biol"},{"key":"2020071614190374500_R48","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/bj2930305","article-title":"Regulated exocytosis.","volume":"293","author":"Burgoyne","year":"1993","journal-title":"Biochem J"},{"key":"2020071614190374500_R49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0014-5793(93)81707-7","article-title":"Rab11, a small GTPase associated with both constitutive and regulated secretory pathways in PC 12 cells.","volume":"334","author":"Urbe","year":"1993","journal-title":"FEBS Lett"},{"key":"2020071614190374500_R50","first-page":"G187","article-title":"Enrichment of rab11, a small GTP-binding protein, in gastric parietal cells","volume":"267","author":"Goldenring","year":"1994","journal-title":"Am J Physiol"},{"key":"2020071614190374500_R51","first-page":"G515","article-title":"Rab 11 is an apically located small GTP-binding protein in epithelial tissues","volume":"270","author":"Goldenring","year":"1996","journal-title":"Am J Physiol"},{"key":"2020071614190374500_R52","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1083\/jcb.135.4.913","article-title":"Rab 11 regulates recycling through the pericentriolar recycling endosome.","volume":"135","author":"Ullrich","year":"1996","journal-title":"J Cell Biol"},{"key":"2020071614190374500_R53","doi-asserted-by":"crossref","first-page":"6187","DOI":"10.1073\/pnas.95.11.6187","article-title":"Hydrolysis of GTP on rab 11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes.","volume":"95","author":"Ren","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190374500_R54","doi-asserted-by":"crossref","first-page":"6535","DOI":"10.1073\/pnas.94.12.6535","article-title":"Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium.","volume":"94","author":"Cooke","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614190374500_R55","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1210\/endo.140.1.6448","article-title":"Tissue compartment-specific estrogen receptor \u03b1 participation in the mouse uterine epithelial secretory response.","volume":"140","author":"Buchanan","year":"1999","journal-title":"Endocrinology"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/13\/6\/993\/10715544\/mend0993.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/13\/6\/993\/10715544\/mend0993.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:26:12Z","timestamp":1647908772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/13\/6\/993\/2741864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,6,1]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1999,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/mend.13.6.0287","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,6,1]]}}}