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Am J Physiol Cell Physiol 278: C689-C696, 2000;
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Vol. 278, Issue 4, C689-C696, April 2000

Involvement of estrogen receptors alpha  and beta  in the regulation of cervical permeability

George I. Gorodeski1,2 and Dipika Pal1

Departments of 1 Reproductive Biology, and 2 Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Estrogen increases the permeability of cultured human cervical epithelia (Gorodeski, GI. Am J Physiol Cell Physiol 275: C888-C899, 1998), and the effect is blocked by the estrogen receptor modulators ICI-182780 and tamoxifen. The objective of the study was to determine involvement of estrogen receptor(s) in mediating the effects on permeability. In cultured human cervical epithelial cells estradiol binds to high-affinity, low-capacity sites, in a specific and saturable manner. Scatchard analysis revealed a single class of binding sites with a dissociation constant of 1.3 nM and binding activity of ~0.5 pmol/mg DNA. Estradiol increased the density of estrogen-binding sites in a time- and dose-related manner (half time approx  4 h, and EC50 approx  1 nM). RT-PCR assays revealed the expression of mRNA for the estrogen receptor alpha  (alpha ER) and estrogen receptor beta  (beta ER). Removal of estrogen from the culture medium decreased and treatment with estrogen increased the expression of alpha ER and beta ER mRNA. In cells not treated with estrogen, ICI-182780 and tamoxifen increased beta ER mRNA. In cells treated with estrogen, neither ICI-182780 nor tamoxifen had modulated significantly the increase in alpha ER or beta ER mRNA. The transcription inhibitor actinomycin D blocked the estrogen-induced increase in permeability, and it abrogated the estradiol-induced increase in estrogen binding sites. These results suggest that the estrogen-dependent increase in cervical permeability is mediated by an alpha ER-dependent increase in transcription.

human; cervical cells; epithelium; transepithelial transport; cervical mucus; transcription; ICI-182780; tamoxifen


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