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Submitted on June 27, 2004
Accepted on October 7, 2004
Departments of Reproductive Biology, Physiology and Biophysics, and Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio
* To whom correspondence should be addressed.
George I. Gorodeski, E-mail: gig{at}cwru.edu
The objective of the study was to understand age-related contributions of the resistance of the intercellular tight junctions (RTJ) and of the resistance of the lateral intercellular space (RLIS) to the transcervical - transvaginal permeability. The experiments used normal human Ectocervical Epithelial Cells (hECE) obtained from women ages 36-65. Twenty-four hours treatment of cells with 10 nM 17
-estradiol decreased the RLIS, while longer treatments were required to decrease The RTJ. Aging had no effect on baseline- or on the estrogen-decrease in RTJ, but it blocked both baseline- and the estrogen-decrease in RLIS. Actin assays showed age-related decrease in the fraction of monomeric G-actin, and attenuation of sodium-nitroprusside - induced increase in G-actin. These results suggest that the aging-related diminished capacity of hECE cells to remodel cellular actin from polymerized actin toward monomeric G-actin confers increased cell rigidity and therefore increased RLIS. Therefore, the hypoestrogenism-related decrease in RTJ and the hypoestrogenism- and aging-related increase in RLIS could be the cellular mechanisms of decreased permeability that lead to decreased fluid transport and decreased lubrication of the lower genital tract in older postmenopausal women.
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