Affiliation:
1. 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.
Abstract
AbstractThe 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 17β-estradiol–dependent signaling in platelets from adult healthy men. 17β-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 β engagement. We found that estrogen receptor β was membrane-associated in platelets. On treatment with 17β-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. 17β-estradiol did not induce any platelet response directly, but it strongly potentiated the activation of integrin αIIbβ3 and the platelet aggregation induced by subthreshold concentrations of thrombin. These effects were dependent on estrogen receptor β recruitment and were associated with a strong synergistic effect with thrombin on Src activation. Taken together, these results indicate that 17β-estradiol can modulate platelet function by exercising a proaggregating role.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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