Abstract
17β-estradiol(E2)is thought to play a pivotal role in regulating female cardiovascular, skeletal, and mental health. The vascular endothelium is a continuous cellular monolayer which forms the luminal lining and governs the homeostatic state of all blood vessels. E2 is believed to prevent endothelial dysfunction that is otherwise characteristic of the early and reversible phase of many forms of vascular pathology 1. A vast majority of these protective actions are directly and indirectly manifested by augmentation of the bioavailability of nitric oxide (NO), due primarily to acute and chronic activation of endothelial nitric oxide synthase (eNOS). In this review, we will emphasize the results from our laboratory with respect to membrane estrogen receptor (ER)-mediated rapid signaling in vascular endothelial cells (EC). There have been important and related studies published by other groups and are presented elsewhere in this book. Readers are referred to the pertinent chapter for additional excellent references.
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References
Vapaatalo H, Mervaala E. Clinically important factors influencing endothelial function. Med Sci Monit. 2001;7:1075–85.
Pietras RJ, Szego CM. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature. 1977;265:69–72.
Caulin-Glaser T, Garcia-Cardena G, Sarrel P, Sessa WC, Bender JR. 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res. 1997;81:885–92.
Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender J. Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. J Biol Chem. 2000;275:5026–5030.
Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999;399:597–601.
McCabe TJ, Fulton D, Roman LJ, Sessa WC. Enhanced Electron Flux and Reduced Calmodulin Dissociation May Explain “Calcium-independent” eNOS Activation by Phosphorylation. J Biol Chem. 2000;275:6123–6128.
Bernier SG, Haldar S, Michel T. Bradykinin-regulated interactions of the mitogen-activated protein kinase pathway with the endothelial nitric-oxide synthase. J Biol Chem. 2000;275:30707–15.
Chen Z, Yuhanna IS, Galcheva-Gargova Z, Karas RH, Mendelsohn ME, Shaul PW. Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. J Clin Invest. 1999;103:401–6.
Haynes MP, Sinha D, Russell KS, Collinge M, Fulton D, Morales-Ruiz M, Sessa WC, Bender JR. Membrane estrogen receptor engagement activates endothelial nitric oxide synthase via the PI3-kinase-Akt pathway in human endothelial cells. Circ Res. 2000;87:677–82.
Russell K, Haynes M, Sinha D, Clerisme E, Bender J. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci USA. 2000;97:5930–5935.
Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, Liao JK. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature. 2000;407:538–41.
Fontana J, Fulton D, Chen Y, Fairchild TA, McCabe TJ, Fujita N, Tsuruo T, Sessa WC. Domain mapping studies reveal that the M domain of hsp90 serves as a molecular scaffold to regulate Akt-dependent phosphorylation of endothelial nitric oxide synthase and NO release. Circ Res. 2002;90:866–73.
Hawkins MB, Thornton JW, Crews D, Skipper JK, Dotte A, Thomas P. Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts. Proc Natl Acad Sci USA. 2000;97:10751–6.
Rubanyi GM, Freay AD, Kauser K, Sukovich D, Burton G, Lubahn DB, Couse JF, Curtis SW, Korach KS. Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption. J Clin Invest. 1997;99:2429–2437.
Chambliss KL, Yuhanna IS, Mineo C, Liu P, German Z, Sherman TS, Mendelsohn ME, Anderson RG, Shaul PW. Estrogen receptor alpha and endothelial nitric oxide synthase are organized into a functional signaling module in caveolae. Circ Res. 2000;87:E44–52.
Pendaries C, Darblade B, Rochaix P, Krust A, Chambon P, Korach KS, Bayard F, Arnal JF. The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Proc Natl Acad Sci U S A. 2002;99:2205–10.
Bauer J, Margolis M, Schreiner C, Edgell CJ, Azizkhan J, Lazarowski E, Juliano RL. In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins. J Cell Physiol. 1992;153:437–49.
Flouriot G, Brand H, Denger S, Metivier R, Kos M, Reid G, Sonntag-Buck V, Gannon F. Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1. Embo J. 2000;19:4688–700.
Woodman SE, Schlegel A, Cohen AW, Lisanti MP. Mutational analysis identifies a short atypical membrane attachment sequence (KYWFYR) within caveolin-1. Biochemistry. 2002;41:3790–5.
Schlegel A, Wang C, Pestell RG, Lisanti MP. Ligand-independent activation of oestrogen receptor alpha by caveolin-1. Biochem J. 2001;359:203–10.
Razandi M, Oh P, Pedram A, Schnitzer J, Levin ER. ERs associate with and regulate the production of caveolin: implications for signaling and cellular actions. Mol Endocrinol. 2002;16:100–15.
Chambliss KL, Yuhanna IS, Anderson RG, Mendelsohn ME, Shaul PW. ERbeta Has Nongenomic Action in Caveolae. Mol Endocrinol. 2002;16:938–46.
Haynes MP, Li L, Russell KS, Bender JR. Rapid vascular cell responses to estrogen and membrane receptors. Vase Pharmacol. 2002;38:99–108.
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Lei, L., Haynes, M.P., Bender, J.R. (2003). Estrogen-Stimulated, Membrane-Initiated Receptor-Ligand Interactions in Vascular Cells. In: Watson, C.S. (eds) The Identities of Membrane Steroid Receptors. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0339-2_5
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DOI: https://doi.org/10.1007/978-1-4615-0339-2_5
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