title: Role of estrogen receptor beta in uterine stroma and epithelium: Insights from estrogen receptor beta-/- mice.
abstract: In this study, we compared the uterine tissue of estrogen receptor (ER)beta(-/-) mice and their WT littermates for differences in morphology, proliferation [the percentage of labeled cells 2 h after BrdUrd injection and EGF receptor (EGFR) expression], and differentiation (expression of progesterone receptor, E-cadherin, and cytokeratins). In ovariectomized mice, progesterone receptor expression in the uterine epithelium was similar in WT and ERbeta(-/-) mice, but E-cadherin and cytokeratin 18 expression was lower in ERbeta(-/-) mice. The percentage of cells in S phase was 1.5% in WT mice and 8% in ERbeta(-/-) mice. Sixteen hours after injection of 17beta-estradiol (E(2)), the number of BrdUrd-labeled cells increased 20-fold in WT mice and 80-fold in ERbeta(-/-) mice. Although ERalpha was abundant in intact mice, after ovariectomy, ERalpha could not be detected in the luminal epithelium of either WT or ERbeta(-/-) mice. In both untreated and E(2)-treated mice, ERalpha and ERbeta were colocalized in the nuclei of many stromal and glandular epithelial cells. However, upon E(2) + progesterone treatment, ERalpha and ERbeta were not coexpressed in any cells. In WT mice, EGFR was located on the membranes and in the cytoplasm of luminal epithelium, but not in the stroma. In ERbeta(-/-) mice, there was a marked expression of EGFR in the nuclei of epithelial and stromal cells. Upon E(2) treatment, EGFR on cell membranes was down-regulated in WT but not in ERbeta(-/-) mice. These findings reveal an important role for ERbeta in response to E(2) and in the organization, growth, and differentiation of the uterine epithelium.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, S-141 86 Novum, Sweden.
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.forename: Haruko
authors.initials: H
authors.lastname: Hiraike
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okinaga
authors.forename: Otabek
authors.initials: O
authors.lastname: Imamov
authors.forename: Rodrigo P A
authors.initials: RP
authors.lastname: Barros
authors.forename: Andrea
authors.initials: A
authors.lastname: Morani
authors.forename: Yoko
authors.initials: Y
authors.lastname: Omoto
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D014599:Uterus / Q000166:cytology / Q000378:metabolism*
chemical_list: D015820:Cadherins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D066246:ErbB Receptors