TitleEstradiol induces E-cadherin degradation in mouse uterine epithelium during the estrous cycle and early pregnancy
Publication TypeJournal Article
Year of Publication1996
AuthorsPotter, SW, Caza, G, Morris, JE
JournalJournal of Cellular Physiology
Type of ArticleJournal Article

Mouse uterine epithelium is a tissue that undergoes cyclic endocrine-regulated cell dissociation and regeneration. It shows a dramatic cell loss following normal estrus. If pregnancy ensues, cell loss is averted during the first 2.5-3.5 days. However, this is followed by a precipitous loss of basal-lateral cell adhesion and apoptosis in preparation for blastocyst invasion. By comparing epithelia isolated by protease treatment, we show that a reduction of lateral cell adhesion is a primary event in these instances of normal tissue loss. It was readily induced in ovariectomized adult and immature mice by injections of estradiol (E(2)), and to some extent also by progesterone (P-4). The reduction of lateral adhesion induced by including ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in the isolation medium mimicked and was additive to the effect of E(2) injection. However, the E(2) effect was different in not being prevented by adding Ca2+. The E(2) effect also was mimicked by the action on isolated epithelium of monoclonal antibody against the calcium-dependent cell adhesion molecule, E-cadherin, suggesting that inactivation of E-cadherin was induced by E(2). In detergent extracts of estrous and metestrous epithelium there was an increase in 80-kDa extracellular domain of E-cadherin relative to the intact 120-kDa molecule. The loss of adhesion between 3.5 and 4.5 days of pregnancy was associated with a loss of both intact membrane-associated 120-kDa E-cadherin and cleavage products. Cleavage of 80-kDa E-cadherin was uniquely induced by E(2) in ovariectomized adult and immature mice; P-4 was without effect. The cleavage of E-cadherin correlated with increased basal accumulation of E-cadherin antigen in estrous and E(2)-injected mice and a loss of both basal and lateral antigen at 4.5 days of pregnancy. Only the E-cadherin antigen within junctional complexes appeared unaffected. The data are consistent with the hypothesis that the cyclic and pregnancy-dependent disruption of uterine epithelial integrity are promoted by E(2)-dependent modification of E-cadherin, including its extracellular cleavage. (C) 1996 Wiley-Liss, Inc.

URL<Go to ISI>://WOS:A1996VJ73000001