Aging and estrogen effects on transcervical-transvaginal epithelial permeability.
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 17beta-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.
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gig@cwru.edu
George I
GI
Gorodeski
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010539:Permeability; D014621:Vagina / Q000378:metabolism*
D000199:Actins; D004967:Estrogens