Role of estrogen receptor beta in colonic epithelium.
Several papers report that the colon is one of the tissues regulated by estrogen receptor (ER)beta. To better understand the physiological role of ERbeta in colonic tissue, we have compared morphology, proliferation, and differentiation of colonic epithelium in ERbeta-/- mice and WT littermates. BrdUrd labeling revealed that the number of proliferating cells was higher in ERbeta-/- mice and that the migration of labeled cells toward the luminal surface was faster in ERbeta-/- mice than in WT littermates. Additionally, in the absence of ERbeta, there was a decrease in apoptosis, which was measured by immunohistochemical staining of cleaved caspase-3. The state of differentiation of the colonic epithelial cells was studied by using epithelial markers. In ERbeta-/- mice, there was a significant decrease in the expression of the differentiation marker cytokeratin (CK)20 and in the cellular adhesion molecules alpha-catenin (an adherens junction protein) and plectin (a hemidesmosomal protein). These changes were also evident by electron microscopy as abnormalities in tight junctions and in the number and shape of desmosomes in ERbeta-/- mice. These findings suggest a role for ERbeta in the organization and architectural maintenance of the colon. Furthermore, our results indicate that the rapidly proliferating cells of the colonic epithelium in ERbeta-/- mice are lost by increased shedding and not by increased apoptosis. In this way, hyperproliferative cells that lack ERbeta do not form hyperplastic lesions and do not accumulate in the superficial epithelium.
Department of Biosciences and Nutrition, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden.
Osamu
O
Wada-Hiraike
Otabek
O
Imamov
Haruko
H
Hiraike
Kjell
K
Hultenby
Thomas
T
Schwend
Yoko
Y
Omoto
Margaret
M
Warner
Jan-Ake
JA
Gustafsson
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D003106:Colon / Q000166:cytology* / Q000502:physiology; D003896:Desmosomes / Q000235:genetics / Q000648:ultrastructure*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology; D053554:Keratin-20; D007633:Keratins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D019108:Tight Junctions / Q000235:genetics / Q000648:ultrastructure*; D051178:alpha Catenin / Q000378:metabolism
D047629:Estrogen Receptor beta; D053554:Keratin-20; D051178:alpha Catenin; D007633:Keratins