title: Canonical Wnt signaling is critical to estrogen-mediated uterine growth.
abstract: Major biological effects of estrogen in the uterus are thought to be primarily mediated by nuclear estrogen receptors, ERalpha and ERbeta. We show here that estrogen in an ER-independent manner rapidly up-regulates the expression of Wnt4 and Wnt5a of the Wnt family and frizzled-2 of the Wnt receptor family in the mouse uterus. One of the mechanisms by which Wnts mediate canonical signaling involves stabilization of intracellular beta-catenin. We observed that estrogen treatment prompts nuclear localization of active beta-catenin in the uterine epithelium. We also found that adenovirus mediated in vivo delivery of SFRP-2, a Wnt antagonist, down-regulates estrogen-dependent beta-catenin activity without affecting some of the early effects (water imbibition and angiogenic markers) and inhibits uterine epithelial cell growth, suggesting that canonical Wnt signaling is critical to estrogen-induced uterine growth. Our present results provide evidence for a novel role of estrogen that targets early Wnt/beta-catenin signaling in an ER-independent manner to regulate the late uterine growth response that is ER dependent.
authors.affiliation: Department of Pediatrics, D-4105 Medical Center North, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232-2678, USA.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Hou
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.forename: Meiling
authors.initials: M
authors.lastname: Li
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Das
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000502:physiology; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*; D014162:Transfection; D014599:Uterus / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein; D051176:beta Catenin; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D003598:Cytoskeletal Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D051157:Frizzled Receptors; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D015534:Trans-Activators; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein; D051176:beta Catenin; C495267:CTNNB1 protein, mouse; C489743:Fzd2 protein, mouse; C491628:Sfrp2 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C555582:Wnt4 protein, mouse; C438615:Wnt5a protein, mouse