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.
1. Renkin EM. Cellular and intercellular transport pathways in exchange vessels. Am Rev Respir Dis1992;146:528-531.
2.
2. Clough, G. Relationship between microvascular permeability and ultrastructure. Prog Biophys Mol Biol1991;55:47-69.
3.
3. Bassenge E. Endothelial function in different organs. Prog Cardivoasc Dis1996;39:209-228.
4.
4. Dejana E, Corada M. Lampugnani MG. Endothelial cell-to-cell junctions. FASEB J1995;9:910-918.
5.
5. Leach L, Fifth JA. Structure and permeability of human placental microvasculature. Microsc Res Tech1997;38:137-144.
6.
6. Michel CC. Transport of macromolecules through microvascular walls. Cardivoasc Res1996;32:644-653.
7.
7. Gorodeski GI, Romero MF, 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. Differentiation1994;56:107-118.
8.
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 Physiol1995;269:C870-C877.
9.
9. Gorodeski GI, Peterson D, De Santis BJ, Hopfer U. Nucleotide-receptor mediated decrease of tight-junctional permeability in cultured human cervical epithelium. Am J Physiol1996;270:C1715-C1725.
10.
10. Gorodeski GI, Wenwu J, Hopfer U. Extracellular Ca2+ directly regulates tight junctional permeability in the human cervical cell line CaSki. Am J Physiol1997;272:C511-C524.
11.
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 Physiol1995;430:145-147.
12.
12. Ussing HH, Zerahn K. Active transport of sodium as the source of electric current in the short-circuited isolated frog skin. Acta Physiol Scand1951;23:110-127.
13.
13. Reuss L. Tight junction permeability to ions and water, In: Cereijido M, ed. Tight-junctions. Boca Raton, Florida: CRC Press, 1991;49-66.
14.
14. Stachenfeld NS, DiPietro L, Palter SF, Nadel ER. Estrogen influences osmotic secretion of AVP and body water balance in postmenopausal women. Am J Physiol1998;274:R187-R195.
15.
15. Pecins-Thompson M, Keller-Wood M. Effects of progesterone on blood pressure, plasma volume, and responses to hypotension. Am J Physiol1997;272:R377-R385.
16.
16. Ziats NP, Anderson JM. Human vascular endothelial cell attachment and growth inhibition by type V collagen. J Vas Surg1993;17:710-718.
17.
17. Gorodeski GI, Eckert RL, Utian WH, Rorke EA. Maintenance of in vivo-like keratin expression, sex steroid responsiveness and estrogen receptor expression in cultural human ectocervical epithelial cells. Endocrinology1990;126:399-406.
18.
18. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J. Sequence and expression of human estrogen receptor DNA. Science1986;231:1150-1154.
19.
19. Kupier GGJM, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors α and β. Endocrinology1997;138:863-869.
20.
20. Siegel S. Nonparametric statistics for the behavioral sciences. London: McGraw-Hill, 1956.
21.
21. Tucker VL, Victorino GP. Methods for studying microvascular barrier function in ischemia-reperfusion injury. Shock1997;8:8-15.
22.
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 Natl Acad Sci USA1986;83:2496-2501.
23.
23. Wakeling AE, Bowler J. ICI 182,780, a new antioestrogen with clinical potential. J Steroid Biochem Mol Biol1992;43:173-177.
24.
24. Furuse M, Hirase T, Ioth M, et al: Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol1993;123:1777-1788.
25.
25. Stuart RO, Sun A, Panichas M, Hebert SC, Brenner BM, Nigam SK. Critical role for intracellular calcium in tight junction biogenesis. J Cell Physiol1994;159:423-433.
26.
26. Stuart RO, Sun A, Bush KT, Nigam SK. Dependence of epithelial intercellular junction biogenesis on thapsigargin-sensitive intracellular calcium stores. J Biol Chem1996;271:13636-13641.
27.
27. Hangxin L, Pozmansky MJ. Characterization of the ZO-1 protein in endothelial and other cell lines. J Cell Sci1990;97:231-237.
28.
28. Anderson JM, Balda MS, Fanning AS. The structure and regulation of tight junctions. Curr Opin Cell Biol1993;5:772-778.
29.
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 Biol1994;124:101-105.
30.
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. Steroids1997;62:268-303.
31.
31. Kimm SS, McGowan KA, Hubchak SC, et al. Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation1996;94:1402-1407.
32.
32. Venkov CD, Rankin AB, Vaughan DE. Identification of authentic estrogen recetor in cultured endothelial cells: A potential mechanism for steroid hermone regulation of endothelial function. Circulation1996;94:727-733.
33.
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 Invest1997;4:316-324.
34.
34. Conger JD, Weil JV. Abnormal vascular function following ischemia-reperfusion injury. J Invest Med1995;43:431-442.
35.
35. Ward BJ, Firth JA. Effect of hypoxia on endothelial morphology and interendothelial junctions in the isolated perfused rat heart. J Mol Cell Cardiol1989;21:1337-1347.
36.
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: Partheon, 1997:402-418.
37.
37. Kim YD, Chen B, Beauregard J, et al. 17-beta-Estradiol prevents dysfunction of canine coronary endothelium and myocardium and reperfusion arrhythmias after brief ischemia/reperfusion. Circulation1996;94:2901-2908.
38.
38. Levy MN, Utian WH, Tang T, Goldfaro J, Gorodeski GI. Effects of estrogen on cardiac stunning in female rabbits (abstract). Menopause1997;4:246(S-2)-246(S-2).
39.
39. Jennings RB, Steenbergen C Jr, Reimer KA. Myocardial ischemia and reperfusion. Monogr Pathol1995;37:47-80.
