Estrogen modulation of epithelial permeability in cervical-vaginal cells of premenopausal and postmenopausal women

In Brief Objective: To understand how menopause affects estrogen regulation of epithelial permeability. Design: Experimental study using human normal epithelial vaginal-ectocervical cells obtained from premenopausal and postmenopausal women. Endpoints were paracellular permeability (determined in terms of the resistance of the lateral intercellular space [RLIS] and tight junctions [RTJ]); cellular G-actin; nonmuscle myosin type II-B (NMMII-B) filamentation and magnesium-adenosine triphosphatase activity; and occludin expression (in terms of expression of the functional 65-kd and truncated 50-kd forms). Results: Estrogen induced an early transient decrease in RLIS that correlated in time with increases in cellular G-actin and NMMII-B magnesium-adenosine triphosphatase activity and with decreases in NMMII-B filamentation and a slower decrease in RTJ that correlated with up-regulation of the 50-kd form of occludin. Estrogen modulation of G-actin NMMII-B and occludin could be described in terms of interaction with the estrogen receptor mechanism. The potency of estrogen effects was similar in cells of premenopausal and postmenopausal women, but the effects occurred earlier in cells of premenopausal women. RLIS returned to baseline faster in cells of postmenopausal women, and the effect was associated with faster reversal of estrogen changes in NMMII-B despite the continued presence of estrogen in the culture medium, suggesting that desensitization of the actin-myosin effects to estrogen actions occur distal to the estrogen receptor. Conclusions: The results suggest that the transient estrogen decrease in RLIS is mediated by modulation of actomyosin, and it is affected by the aging process. In contrast, the late persistent decrease in RTJ is mediated by occludin degradation and is unrelated to aging. The objective of the study was to understand how menopause affects estrogen regulation of epithelial permeability through modulation of the paracellular resistance (ie, the resistance of the lateral intercellular space and the tight junctional resistance). The results suggest that the estrogen transient decrease in the resistance of the lateral intercellular space is mediated by modulation of the actomyosin and is affected by occludin degradation and is unrelated to aging.