Effect of estradiol on mouse uterine epithelial cell transepithelial resistance (TER).
OBJECTIVE
The effects of estradiol on epithelial cell function in the uterus may either be direct or indirect through the paracrine effects of underlying stromal cells. The aim of this study was to test whether estradiol-17beta (E(2)) acts directly to regulate uterine epithelial cell monolayer integrity.


METHODS
Mouse uterine epithelial cells were isolated and grown on cell culture inserts to form confluent, polarized monolayers, as indicated by the development of high transepithelial resistance (TER).


RESULTS
When polarized epithelial cells were treated with E(2), TER was significantly decreased within 24 hr of exposure. Epithelial cells remained hormonally responsive in culture for at least 10 days. In contrast to estradiol, incubation with progesterone, cortisol, aldosterone, and DHT had no effect on uterine epithelial cell TER. The ability of E(2) to decrease TER was inhibited following co-incubation with ICI 182,780, a pure estrogen receptor antagonist. To further investigate the mechanism involved in estradiol-induced decreases in TER, we tested the effect of TAPI-0, an inhibitor of matrix metalloproteinases. Our findings indicate that TAPI-0 reversed the inhibitory effect of E(2) on TER.


CONCLUSIONS
These studies demonstrate that epithelial monolayer integrity is directly influenced by E(2) and ER mediated. Further, it suggests that the mechanism through which estradiol decreases TER is mediated by matrix metalloproteinases.
Grant-Tschudy
Katherine S
KS
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA. katherine.grant@dartmouth.edu
Wira
Charles R
CR
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D014599:Uterus / Q000166:cytology / Q000187:drug effects*
D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004958:Estradiol; D020782:Matrix Metalloproteinases