The hormonal regulation of cadherin-11 expression in the human endometrium

The human endometrium undergoes cyclic proliferation, differentiation, and shedding in response to 17R-estradiol and progesterone. To date, the cellular mechanisms by which these gonadal steroids regulate the formation and organisation of this dynamic tissue remain poorly understood. We have recently determined that cadherin-11, a type 2 classical cadherin, is spatiotemporally expressed in the human endometrium during the menstrual cycle. In particular, cadherin-11 is first detected in the endometrial stroma during the secretory phase of the menstrual cycle with maximum expression levels being observed in the decidua of pregnancy. As the cadherins play critical roles in the formation and organisation of tissues during embryonic development, we hypothesised that the morphogenetic effects exerted by gonadal steroids on the endometrium may be mediated, at least in part, by their ability to regulate stromal cadherin-11 expression levels. In these studies, we have examined the ability of 176-estradiol, progesterone, and dihydrotestosterone, alone or In combination, to regulate cadherin-11 mRNA and protein expression levels in cultured human endometrial stromal cells. Progesterone, but not estradiol or dihydrotestosterone, increased stromal cadherin-11 mRNA and protein expression levels over time in culture. However, 1 7S-estradiol was capable of potentiating the stimulatory effects of progesterone on stromal cadherin-11 expression. Maximum levels of cadherin-11 were detected in endometrial stromal cells which had undergone decidualisation in response to long term culture in the presence of these two gonadal steroids. Cadherin-11 expression in decidualised endometrial stromal cells was effectively reduced by the antiprogestin RU486, the antiestrogen ICI 182,780, and steroid withdrawal suggesting that the progesterone-mediated increase in stromal cadherin-11 expression was dependent on estrogens. Finally, progesterone increased the levels of the mRNA transcript encoding 6 - catenin, a cadherin-associated cytoplasmic protein, in these primary cell cultures. This is the first demonstration that gonadal steroids are capable of coordinately regulating cadherin-11 and S-catenin expression in a mammalian cell type. Collectively, these studies not only add to our understanding of the cell biology of this novel cadherin subtype but give us insight into the cellular mechanisms by which gonadal steroids regulate the remodeling processes that occur in the endometrium during each menstrual cycle.