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Aging and Estrogen Effects on Transcervical-Transvaginal Epithelial Permeability

Departments of Reproductive Biology, Physiology and Biophysics, and Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Address all correspondence and requests for reprints to: George I. Gorodeski, M.D., Ph.D., University MacDonald Women’s Hospital, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106. 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 (R_TJ) and the resistance of the lateral intercellular space (R_LIS) to the transcervical-transvaginal permeability. The experiments used normal human ectocervical epithelial cells obtained from women aged 36–65 yr. Twenty-four hours of treatment of cells with 10 nM 17ß-estradiol decreased the R_LIS, whereas longer treatments were required to decrease The R_TJ. Aging had no effect on baseline or estrogen decrease in R_TJ, but it blocked both baseline and the estrogen decrease in R_LIS. 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 human ectocervical epithelial cells to remodel cellular actin from polymerized actin toward monomeric G-actin confers increased cell rigidity and therefore increased R_LIS. Therefore, the hypoestrogenism-related decrease in R_TJ and the hypoestrogenism- and aging-related increase in R_LIS 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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