title: Neonatal Estrogen Receptor β Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus.
abstract: Estrogen receptor α (ERα) plays a pivotal role in the mouse uterine and vaginal epithelial cell proliferation stimulated by estrogen, whereas ERβ inhibits cell proliferation. ERβ mRNA is expressed in neonatal uteri and vaginae; however, its functions in neonatal tissues have not been ascertained. In this study, we investigated the ontogenic mRNA expression and localization of ERβ, and its roles in cell proliferation in neonatal uteri and vaginae of ERβ knockout (βERKO) mice. ERβ mRNA and protein were abundant in the uterine and vaginal epithelia of 2-day-old mice and decreased with age. In uterine and vaginal epithelia of 2-day-old βERKO mice, cell proliferation was greater than that in wild-type animals and in uterine epithelia of 90- and 365-day-old βERKO mice. In addition, p27 protein, known as a cyclin-dependent kinase inhibitor, was decreased in the uteri of 90- and 365-day-old βERKO mice. Inhibition of neonatal ERs by ICI 182780 (an ER antagonist) treatment stimulated cell proliferation and decreased p27 protein in the uterine luminal epithelium of 90-day-old mice but not in the vaginal epithelium. These results suggest that neonatal ERβ is important in the persistent inhibition of epithelial cell proliferation with accumulation of p27 protein in the mouse uterus. Thus, suppression of ERβ function in the uterine epithelium during the neonatal period may be responsible for a risk for proliferative disease in adults.
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tanimoto
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
authors.affiliation: Graduate School of Nanobioscience (T.N., Y.T., T.S.), Yokohama City University, Yokohama 236-0027, Japan; Department of Biological Science and Technology (T.N.), Tokyo University of Science, Tokyo 125-8585, Japan; Department of Food and Nutrition (M.T.), Junior College of Aizu, Aizu 965-8570, Japan; Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur (P.C.), Collège de France, 67404 Illkirch, France; Graduate School of Engineering (H.W.), Osaka University, Suita 565-0871, Japan; and Okazaki Institute for Integrative Bioscience (T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000097:blood; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000502:physiology*; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014599:Uterus / Q000502:physiology*; D014621:Vagina / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D036341:Intercellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077267:Fulvestrant; D004958:Estradiol