This Article Full Text Full Text (PDF) Submit a related Letter to the Editor 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 Gorodeski, G. I. Search for Related Content PubMed PubMed Citation Articles by Gorodeski, G. I.

Effects of Menopause and Estrogen on Cervical Epithelial Permeability¹

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

Address 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}po.cwru.edu

The objective of the study was to characterize the effect and explore the mechanisms by which menopause affects paracellular permeability of cultured human cervical epithelium. The experimental system was cultures of human ectocervical epithelial (hECE) cells on filters. Assays included flux measurements of cell-impermeable molecules and determinations of transepithelial electrical conductance. hECE cells of postmenopausal women formed epithelia with lower paracellular permeability than hECE cells of premenopausal women. Treatment with estrogen increased paracellular permeability, but levels remained lower compared to cultures from premenopausal women. Lowering extracellular calcium or treatment with cytochalasin-D, conditions that decrease the tight junctional resistance (R_TJ), increased the permeability, and the relative effects were greater in cells of premenopausal women than in postmenopausal women. Treatment of cells with sn-1,2-dioctanoyl diglyceride, an agent that increases the R_TJ, decreased the permeability, and the relative effect was greater in cells of postmenopausal women than in cells of premenopausal women. Estrogen had no significant effect on the responses to low calcium, cytochalasin-D, or sn-1,2-dioctanoyl diglyceride. Hydrostatic and hypertonic gradients in the subluminal to luminal direction, conditions that decrease the resistance of the lateral intercellular space increased the permeability to a similar degree in cultures of cells from premenopausal and from postmenopausal women. Pretreatment with estrogen augmented the increases in permeability in response to hydrostatic and hypertonic gradients. In cells exposed to low extracellular calcium, hydrostatic gradients had an additive increase in permeability. By extrapolation it was determined that in cultures of postmenopausal women R_TJ contributes 97% to the total paracellular resistance, whereas in hECE cultures of premenopausal women the R_TJ contributes only 84%. These results indicate that after menopause the transcervical paracellular permeability decreases significantly; this can explain the decrease in lubrication of the cervix and vagina in postmenopausal women. Part of the effect is due to lack of estrogen, and it can be reversed by treatment with the hormone. However, most of the effect is unrelated to estrogen and is caused by an increase in R_TJ.

This article has been cited by other articles:

				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]

				G. I. Gorodeski Aging and Estrogen Effects on Transcervical-Transvaginal Epithelial Permeability J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 345 - 351. [Abstract] [Full Text] [PDF]

				R. H. Wasserman Vitamin D and the Dual Processes of Intestinal Calcium Absorption J. Nutr., November 1, 2004; 134(11): 3137 - 3139. [Full Text] [PDF]

				M. Espinosa, G. Noe, C. Troncoso, S.B. Ho, and M. Villalon Acidic pH and increasing [Ca2+] reduce the swelling of mucins in primary cultures of human cervical cells Hum. Reprod., August 1, 2002; 17(8): 1964 - 1972. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski Regulation of transcervical permeability by two distinct P2 purinergic receptor mechanisms Am J Physiol Cell Physiol, January 1, 2002; 282(1): C75 - C83. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski Expression, regulation, and function of P2X4 purinergic receptor in human cervical epithelial cells Am J Physiol Cell Physiol, January 1, 2002; 282(1): C84 - C93. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski Estrogen Biphasic Regulation of Paracellular Permeability of Cultured Human Vaginal- Cervical Epithelia J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4233 - 4243. [Abstract] [Full Text] [PDF]