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Effects of Estrogen on Tight Junctional Resistance in Cultured Human Umbilical Vein Endothelial Cells

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The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

To study the effects of estrogen on transendothelial paracellular permeability in women.

Methods

Human umbilical vein endothelial cells (HUVEC) obtained from women were grown on filters. The paracellular permeability characteristics were determined in terms of changes in the prmeability to the polar acid pyranine (Ppyr) and as changes in the transendothelial electrical resistance (RTE). Tight junctional resistance characteristics were assayed by lowering luminal NaCl and measuring the dilution potential, and were expressed as the ratio of monion mobility uCl/uNa (cation selectivity).

Results

Low extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The former but not the latter condition abolished the endothelium-specific cation selectivity. Treatment with 10 nM of estradiol-17β had no effect on RTE, but it increased the cation selectivity. The effect of estradiol required 1-6 hours’ incubation with the hormone; it was dose dependent and saturable, with a median effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not estriol, could mimic the effect of estradiol, and the estrogen rectpro antagonist ICI-182,780 blocked it.

Conclusion

Cultured HUVEC cells from patent tight junctions. Estrogens increase the cation selectivity across HUVEC cultures. The effect of estrogen may be mediated by an estrogen receptor. These effects may be important for vasculoprotection in cases of sudden changes in ions levels across the capillary wall, such as ischemia or reperfusion.

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References

  1. Renkin EM. Cellular and intercellular transport pathways in exchange vessels. Am Rev Respir Dis 1992; 146: 528–31.

    Article  Google Scholar 

  2. Clough, G. Relationship between microvascular permeability and ultrastructure. Prog Biophys Mol Biol 1991; 55: 47–69.

    Article  CAS  Google Scholar 

  3. Bassenge E. Endothelial function in different organs. Prog Car-diovasc Dis 1996; 39: 209–28.

    Article  CAS  Google Scholar 

  4. Dejana E, Corada M, Lampugnani MG. Endothelial cell-to-cell junctions. EASEB J 1995; 9: 910–8.

    CAS  Google Scholar 

  5. Leach L, Firth JA. Structure and permeability of human placental microvasculature. Microsc Res Tech 1997; 38: 137–44.

    Article  CAS  Google Scholar 

  6. Mithel CC. Transport of macromolecules through microvascular walls. Cardiovasc Res 1996; 32: 644–53.

    Article  Google Scholar 

  7. Gorodeski GI, Romero MP, Hopfer U, Rorke E, Utian WH, Eckert RL. Human uterine cervical epithelial cells grown on permeable support—a new model for the study of differentiation and transepithelial transport. Differentiation 1994; 56: 107–18.

    CAS  PubMed  Google Scholar 

  8. Gorodeski GI, De Santis BJ, Goldfarb J, Utian WH, Hopfer U. Osmolar changes regulate the paracellular permeability of cultured human cervical epithelium. Am J Phvsiol 1995; 269: C870–7.

    Article  CAS  Google Scholar 

  9. Gorodeski GI, Peterson D, De Santis BJ, Hopfer U. Nucleotide-receptor mediated decrease of tight-junctional permeability in cultured human cervical epithehum. Am J Physiol 1996; 270: C1715–25.

    Article  CAS  Google Scholar 

  10. Gorodeski GI, Wenwu J, Hopfer U. Extracellular Ca2+ directly regulates tight junctional permeability in the human cervical cell line CaSki. Am J Physiol 1997; 272: C511–24.

    Article  CAS  Google Scholar 

  11. Tschugguel W, Zhegu Z, Gajdzik L, Maier M, Binder BR, Graf J. High precision measurement of electrical resistance across endothelial cell monolayers. Eur J Physiol 1995; 430: 145–7.

    Article  CAS  Google Scholar 

  12. Ussing HH, Zerahn K. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta Physiol Scand 1951; 23: 110–27.

    Article  CAS  Google Scholar 

  13. Reuss L. Tight junction permeability to ions and water. In: Gereijido, M, ed. Tight-junctions. Boca Raton, Florida: GRC Press, 1991; 49–66.

    Google Scholar 

  14. Stathenfeld NS, DiPietro L, Palter SF, Nadel ER. Estrogen influences osmotic secretion of AVP and body water balance in postmenopausal women. Am J Physiol 1998; 274: R187–95.

    Google Scholar 

  15. Pecins-Thompson M, Keller-Wood M. Effects of progesterone on blood pressure, plasma volume, and responses to hypotension. Am J Physiol 1997; 272: R377–85.

    CAS  PubMed  Google Scholar 

  16. Ziats NP, Anderson JM. Human vascular endothelial cell attachment and growth inhibition by type V collagen. J Vasc Surg 1993; 17: 710–8.

    Article  CAS  Google Scholar 

  17. Gorodeski GI, Eckert RL, Utian WH, Rorke EA. Maintenance of in vivo-like keratin expression, sex steroid responsiveness and estrogen receptor expression in cultured human ectocervical epithelial cells. Endocrinology 1990; 126: 399–406.

    Article  CAS  Google Scholar 

  18. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J. Sequence and expression of human estrogen receptor DNA. Science 1986; 231: 1150–4.

    Article  CAS  Google Scholar 

  19. Kuiper GGJM, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors a and p. Endocrinology 1997; 138: 863–69.

    Article  CAS  Google Scholar 

  20. Siegel S. Nonparametric statistics for the behavioral sciences. London: McGraw-Hill 1956.

    Google Scholar 

  21. Tucker VL, Victonno GP. Methods for studying microvascular barrier function in isthemia-reperfusion injurv. Shock 1997; 8: 8–15.

    Article  CAS  Google Scholar 

  22. Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS. Phenol red in tissue culture medium is a weak estrogen: Implication concerning the study of estrogen-responsive cells in culture. Proc Nad Acad Sci USA 1986; 83: 2496–501.

    Article  CAS  Google Scholar 

  23. Wakeling AE, Bowler j. ICI 182,780, a new antioestrogen with clinical potential. J Steroid Biothem Mol Biol 1992; 43: 173–7.

    Article  CAS  Google Scholar 

  24. Furuse M, Hirase T, Itoh M, et al. Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123: 1777–88.

    Article  CAS  Google Scholar 

  25. Stuart RO, Sun A, Panichas M, Hebert SC, Brenner BM, Nigam SK. Critical role for intracellular calcium in tight junction biogenesis. J Cell Physiol 1994; 159: 423–33.

    Article  CAS  Google Scholar 

  26. Stuart RO, Sun A, Bush KT, Nigam SK. Dependence of epithelial intercellular junction biogenesis on thapsigargin-sensitive intracellular calcium stores. J Biol Thern 1996; 271: 13636–41.

    CAS  Google Scholar 

  27. Hangxin L, Pozmansky MJ. Characterization of the ZO-1 protein m endothlial and other cell hnes. J Cell Sci 1990; 97: 231–7.

    Google Scholar 

  28. Anderson JM, Balda MS, Fanning AS. The structure and regulation of tight junctions. Curr Opin Cell Biol 1993; 5: 772–8.

    Article  CAS  Google Scholar 

  29. Zahraoui A, Joberty G, Arpin M, et al. A small rab GTPase is distributed in cytoplasmic vesicles in non polarized cells but colocalizes with the tight junction marker ZO-1 in polarized epithelial cells. J Cell Biol 1994; 124: 101–5.

    Article  CAS  Google Scholar 

  30. Anstead GM, Carlson KE, Katzenellenbogen JA. The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site. Steroids 1997; 62: 268–303.

    Article  CAS  Google Scholar 

  31. Kim SS, McGowan KA, Hubchak SC, et al. Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circuladon 1996; 94: 1402–7.

    Google Scholar 

  32. Venkov CD, Rankin AB, Vaughan DE. Identificadon of authen-tic estrogen receptor in cultured endothehal cells: A potential mechanism for steroid hormone regulation of endothelial function. Circulation 1996; 94: 727–33.

    Article  CAS  Google Scholar 

  33. Baker VL, Chao VA, Murai JT, Zaloudek CJ. Taylor RN. Human umbilical vessels and cultured umbilical vein endothelial and smooth muscle cells lack detectable protein and mRNA-encoding estrogen receptors. J Soc Gyn Invest 1997; 4: 316–24.

    CAS  Google Scholar 

  34. Conger JD, Weil JV. Abnormal vascular function following isthemia-reperfusion injury. J Invest Med 1995; 43: 431–42.

    CAS  Google Scholar 

  35. Ward BJ, Firth JA. Effect of hypoxia on endothehal morphology and interendothelial juncrions in the isolated perfused rat heart. J Mol Cell Cardiol 1989; 21: 1337–47.

    Article  CAS  Google Scholar 

  36. Gorodeski GI. Mechanisms of action for estrogen in cardio-protection. In: Wren BG, ed. Progress in the management of menopause. Camforth, Lancashire, United Kingdom: Parthenon, 1997: 402–18.

    Google Scholar 

  37. Kim YD, Then B, Beauregard J, et al. 17-beta-Estradiol prevents dysfunction of canine coronary endothelium and myocardium and reperfusion arrhythmias after brief isthemia/reperfusion. Circulation 1996; 94: 2901–8.

    Article  CAS  Google Scholar 

  38. Levy MN, Utian WH, Tang T, Goldfarb J, Gorodeski GL. Effects of estrogen on cardiac stunning in female rabbits (abstract). Menopause 1997; 4: 246(S-2).

    Article  Google Scholar 

  39. Jennings RB, Steenbergen C Jr, Reimer KA. Myocardial isthemia and reperfusion. Monogr Pathol 1995; 37: 47–80.

    CAS  PubMed  Google Scholar 

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Author information

Author notes

  1. Michael M. Cho MD

    Present address: Department of Ob-Gyn, Division of Reproductive Endocrinology and Infertility, USC/LAC, Women’s and Children’s Hospital, Room IM2, 1240 North Mission Road, Los Angeles, CA, 90033, USA

Authors and Affiliations

  1. Departments of Reproductive Biology, Pathology, and Physiology and Biophysic, Case Western Reserve University School of Medicine, Cleverand, Ohio, USA

    Michael M. Cho MD, Nicholas P. Ziats PhD, Fadi W. Abdul-Karim MD, Dipika Pal BS, James Goldfarb MD, Wulf H. Utian MD, PhD & George I. Gorodeski MD, PhD

Authors
  1. Michael M. Cho MD
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  2. Nicholas P. Ziats PhD
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  3. Fadi W. Abdul-Karim MD
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  4. Dipika Pal BS
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  5. James Goldfarb MD
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  6. Wulf H. Utian MD, PhD
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  7. George I. Gorodeski MD, PhD
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Corresponding author

Correspondence to George I. Gorodeski MD, PhD.

Additional information

Supported in part by grants from Bristol Myers Squibb Company (US Phannaceuticals) to G. 1. G., and from the National Institutes of Health, Heart. Lung, and Blood Institute. Grant HL-48771, to N. P. Z. Dr. Alan Wakeling (Zeneca Pharmaceuticals) is acknowl edged for providing the ICI–182,780.

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Cho, M.M., Ziats, N.P., Abdul-Karim, F.W. et al. Effects of Estrogen on Tight Junctional Resistance in Cultured Human Umbilical Vein Endothelial Cells. Reprod. Sci. 5, 260–270 (1998). https://doi.org/10.1177/107155769800500507

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