Vaginal-cervical epithelial permeability decreases after menopause.
OBJECTIVE
To determine the effects of menopause (aging and E) on vaginal-cervical epithelial paracellular permeability.


METHODS
Experimental, basic clinical research.


METHODS
Academic research environment.


METHODS
Premenopausal, perimenopausal, and postmenopausal women, aged 35-65 years.


METHODS
Primary to tertiary cultures of normal human ectocervical epithelial cells on filters. Cells were outgrown from surgically discarded ectocervical minces.


METHODS
Changes in paracellular permeability were determined as changes in transepithelial electrical conductance and pyranine permeability.


RESULTS
[1] Levels of transepithelial electrical conductance and pyranine permeability decreased as women's age advanced. [2] Removal of E from the culture medium decreased paracellular permeability. Treatment of cells in vitro with 10 nmol/L 17beta-E2 increased transepithelial electrical conductance and pyranine permeability, but the effects were additive to the age-related decrease in permeability. [3] Coadministration of 100 nmol/L tamoxifen blocked the E increase in paracellular permeability in cells of both premenopausal and postmenopausal women.


CONCLUSIONS
[1] Aging and E deficiency decrease independently vaginal-cervical epithelial paracellular permeability. [2] The E increase in vaginal-cervical epithelial paracellular permeability in cells of postmenopausal women is mediated by the E receptor. [3] The E increase in vaginal-cervical epithelial paracellular permeability in cells of postmenopausal women is masked by age-related increase in the tight junctional resistance, leading to overall decrease in paracellular permeability.
Gorodeski
G I
GI
Department of Obstetrics and Gynecology, University MacDonald Women's Hospital, Cleveland, Ohio 44106, USA. gig@po.cwru.edu
D000328:Adult; D000375:Aging / Q000502:physiology; D001190:Arylsulfonates / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D008593:Menopause / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014621:Vagina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D001190:Arylsulfonates; D004965:Estrogen Antagonists; D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol; C005047:pyranine