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Blood, 1 January 2005, Vol. 105, No. 1, pp. 115-121. Prepublished online as a Blood First Edition Paper on June 15, 2004; DOI 10.1182/blood-2003-11-3840. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3840v1 105/1/115    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Moro, L. Articles by Sinigaglia, F. Search for Related Content PubMed PubMed Citation Articles by Moro, L. Articles by Sinigaglia, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Nongenomic effects of 17-estradiol in human platelets: potentiation of thrombin-induced aggregation through estrogen receptor and Src kinase Laura Moro, Stefania Reineri, Daniela Piranda, Daniela Pietrapiana, Paolo Lova, Alessandra Bertoni, Andrea Graziani, Paola Defilippi, Ilaria Canobbio, Mauro Torti, and Fabiola Sinigaglia From the Department of Medical Sciences, DISCAFF, University "A. Avogadro," Novara; the Department of Biochemistry, University of Pavia; and the Department of Genetics, Biology and Biochemistry, University of Turin, Italy. The impact of estrogens on the cardiovascular system and their ability to regulate platelet function are matters of controversy. The recent finding that estrogen receptors are expressed in human platelets renders these cells an excellent model for studying the nongenomic effects of these hormones. In this work, we investigated 17-estradiol–dependent signaling in platelets from adult healthy men. 17-estradiol caused the rapid phosphorylation of the tyrosine kinases Src and Pyk2 and the formation of a signaling complex, which included Src, Pyk2, and the phosphatidylinositol 3-kinase. Both these events were dependent on estrogen receptor engagement. We found that estrogen receptor was membrane-associated in platelets. On treatment with 17-estradiol, Src and Pyk2 activation occurred in the membrane fraction but not in the cytosol. In contrast, no significant activation of phosphatidylinositol 3-kinase was detected in estrogen-treated platelets. 17-estradiol did not induce any platelet response directly, but it strongly potentiated the activation of integrin IIb3 and the platelet aggregation induced by subthreshold concentrations of thrombin. These effects were dependent on estrogen receptor recruitment and were associated with a strong synergistic effect with thrombin on Src activation. Taken together, these results indicate that 17-estradiol can modulate platelet function by exercising a proaggregating role. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. C Villar, A. J Hobbs, and A. Ahluwalia Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor J. Endocrinol., June 1, 2008; 197(3): 447 - 462. [Abstract] [Full Text] [PDF] C. E. Holmes, J. C. Huang, T. R. Pace, A. B. Howard, and H. B. Muss Tamoxifen and Aromatase Inhibitors Differentially Affect Vascular Endothelial Growth Factor and Endostatin Levels in Women with Breast Cancer Clin. Cancer Res., May 15, 2008; 14(10): 3070 - 3076. [Abstract] [Full Text] [PDF] A. A. Shanmugam, J. K. Kumar, I. Selvaraj, and V. Selvaraj Hematology of Sloth Bears (Melursus ursinus ursinus) from Two Locations in India J. Wildl. Dis., April 1, 2008; 44(2): 509 - 518. [Abstract] [Full Text] [PDF] S. R. Hammes and E. R. Levin Extranuclear Steroid Receptors: Nature and Actions Endocr. Rev., December 1, 2007; 28(7): 726 - 741. [Abstract] [Full Text] [PDF] K. Ohshiro, S. K. Rayala, M. D. Williams, R. Kumar, and A. K. El-Naggar Biological Role of Estrogen Receptor {beta} in Salivary Gland Adenocarcinoma Cells. Clin. Cancer Res., October 15, 2006; 12(20): 5994 - 5999. [Abstract] [Full Text] [PDF] C. Bolego, E. Vegeto, C. Pinna, A. Maggi, and A. Cignarella Selective Agonists of Estrogen Receptor Isoforms: New Perspectives for Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2192 - 2199. [Abstract] [Full Text] [PDF] M. Jayachandran, K. Karnicki, R. S. Miller, W. G. Owen, K. S. Korach, and V. M. Miller Platelet Characteristics Change With Aging: Role of Estrogen Receptor {beta} J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2005; 60(7): 815 - 819. [Abstract] [Full Text] [PDF]

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