Antisteroidal compounds and steroid withdrawal down-regulate cadherin-11 mRNA and protein expression levels in human endometrial stromal cells undergoing decidualisation in vitro.
The cellular mechanisms by which steroids and antisteroidal compounds modulate the function and/or integrity of the human endometrium remain poorly understood. We recently determined that the expression of the novel cadherin subtype, known as cadherin-11, is tightly regulated in endometrial stromal cells undergoing decidualisation in vivo and in vitro. To determine whether the actions of antisteroids on the endometrium are mediated, at least in part, by their ability to regulate the expression of this cell adhesion molecule, we examined the effects of the antiprogestin RU486 and the antiestrogen ICI 182,780 on cadherin-11 mRNA and protein expression levels in human endometrial stromal cells undergoing decidualisation in vitro. RU486 decreased the levels of the cadherin-11 mRNA transcript and protein species present in these cell cultures in a dose- and time-dependent manner. Similarly, ICI 182,780 was capable of reducing stromal cadherin-11 mRNA and protein expression levels in a dose-dependent manner, suggesting that the progesterone-mediated increase in cadherin-11 expression levels in human endometrial cells undergoing decidualisation in vitro is dependent on the presence of estrogens. Cadherin-11 expression levels also were reduced in endometrial stromal cell cultures subjected to progesterone withdrawal, an in vitro model for menstrual breakdown. These studies not only give us useful insight into the mechanism(s) by which progesterone regulates stromal cadherin-11 expression, but they strengthen our hypothesis that this cell adhesion molecule plays a central role in the remodeling processes that occur in the human endometrium in response to fluctuations in the levels of gonadal steroids.
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada.
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D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D013256:Steroids / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D015820:Cadherins; D006727:Hormone Antagonists; D012333:RNA, Messenger; D013256:Steroids; C086960:osteoblast cadherin; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol