This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeng, R. Articles by Gorodeski, G. I. Search for Related Content PubMed PubMed Citation Articles by Zeng, R. Articles by Gorodeski, G. I.

Estrogen Abrogates Transcervical Tight Junctional Resistance by Acceleration of Occludin Modulation

Departments of Reproductive Biology (R.Z., X.L., G.I.G.), Physiology and Biophysics (G.I.G.), and Oncology (G.I.G.), Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Address all correspondence and requests for reprints to: George I. Gorodeski, M.D., Ph.D., University MacDonald Women’s Hospital, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106. E-mail: gig{at}cwru.edu.

The present study explored the effects of estrogen on transcervical tight-junctional resistance (R_TJ) and the mechanisms involved. Treatment of cultured human cervical epithelial cells with 17ß-estradiol decreased in a time- and dose-related manner the R_TJ. Estrogen had no significant effect on the expression of E-Cadherin, zonula-occluden-1, or Claudin-4. In contrast, 17ß-estradiol modulated expression of the transmembrane tight-junctional protein occludin: at low concentrations (1 and 10 nM) estradiol increased the density of occludin 65-kDa form but at the higher concentration of 100 nM estradiol induced only a mild 2-fold increase in the density of this form. Estradiol also increased the expression of occludin 50-kDa form in a dose-related manner. The R_TJ and occludin effects of estradiol were reversible and could be blocked by tamoxifen but not progesterone. The present results rule out estrogen modulation of occludin transcription. In contrast, the results suggest that the occludin effects of estrogen involve posttranslational up-regulation of occludin turnover, including synthesis and degradation. The effects of estrogen on occludin expression were compared with those of proteinase-K, plasmin, and matrix-metaloproteinase-2 (all added extracellularly). The three proteinases abrogated irreversibly the R_TJ and induced expression de novo of occludin low-molecular-weight forms. The latter, however, differed from the effect of estrogen, which generated only a single 50-kDa form. Collectively, the present data suggest that the occludin 50-kDa form is an estrogen-specific-induced occludin isoform and that the mechanism of estrogen-abrogation of transcervical R_TJ involves occludin modulation.

This article has been cited by other articles:

				W. K. Sumanasekera, G. U. Sumanasekera, K. A. Mattingly, S. M. Dougherty, R. S. Keynton, and C. M. Klinge Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity Am J Physiol Cell Physiol, August 1, 2007; 293(2): C566 - C573. [Abstract] [Full Text] [PDF]

				B. C. Timmons, S. M. Mitchell, C. Gilpin, and M. S. Mahendroo Dynamic Changes in the Cervical Epithelial Tight Junction Complex and Differentiation Occur during Cervical Ripening and Parturition Endocrinology, March 1, 2007; 148(3): 1278 - 1287. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski Estrogen Modulation of MgATPase Activity of Nonmuscle Myosin-II-B Filaments Endocrinology, January 1, 2007; 148(1): 279 - 292. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski Estrogen Decrease in Tight Junctional Resistance Involves Matrix-Metalloproteinase-7-Mediated Remodeling of Occludin Endocrinology, January 1, 2007; 148(1): 218 - 231. [Abstract] [Full Text] [PDF]

				X. Li, L. Zhou, and G. I. Gorodeski Estrogen Regulates Epithelial Cell Deformability by Modulation of Cortical Actomyosin through Phosphorylation of Nonmuscle Myosin Heavy-Chain II-B Filaments Endocrinology, November 1, 2006; 147(11): 5236 - 5248. [Abstract] [Full Text] [PDF]

				X. Li, L. Zhou, Y.-H. Feng, F. W. Abdul-Karim, and G. I. Gorodeski The P2X7 Receptor: A Novel Biomarker of Uterine Epithelial Cancers. Cancer Epidemiol. Biomarkers Prev., October 1, 2006; 15(10): 1906 - 1913. [Abstract] [Full Text] [PDF]

				M. C Fleisch, C. A Maxwell, and M.-H. Barcellos-Hoff The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs. Endocr. Relat. Cancer, June 1, 2006; 13(2): 379 - 400. [Abstract] [Full Text] [PDF]

				L. Zhu, X. Li, R. Zeng, and G. I. Gorodeski Changes in Tight Junctional Resistance of the Cervical Epithelium Are Associated with Modulation of Content and Phosphorylation of Occludin 65-Kilodalton and 50-Kilodalton Forms Endocrinology, February 1, 2006; 147(2): 977 - 989. [Abstract] [Full Text] [PDF]