Estrogen modulation of epithelial permeability in cervical-vaginal cells of premenopausal and postmenopausal women.
OBJECTIVE
To understand how menopause affects estrogen regulation of epithelial permeability.


METHODS
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.
Gorodeski
George I
GI
Department of Reproductive Biology, Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA. gig@cwru.edu
D000328:Adult; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology* / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D017697:Premenopause; D019108:Tight Junctions / Q000187:drug effects; D014621:Vagina / Q000166:cytology* / Q000187:drug effects
D004958:Estradiol