title: Transdermal 17-beta estradiol replacement therapy reduces megakaryocyte GPVI expression.
abstract: The platelet-collagen interaction is a critical early event in arterial thrombus formation, and platelet GPVI is the major activating receptor for collagen. We have previously used a mouse model to demonstrate that the estrogen effects on platelets depend upon the agonist, estrogen formulation and route of administration. In the current study we used a model of transdermal estradiol (E2) administration to ovariectomized mice to address the potential inhibitory effects of E2 on platelet GPVI. Platelet GPVI expression was reduced after transdermal E2 replacement therapy (p <or= 0.001) but no evidence of GPVI shedding was found when platelets were directly incubated with E2. In addition, significantly reduced GPVI-mediated fibrinogen binding and aggregation were observed in platelets from mice subjected to 9 days or longer of in vivo E2 treatment, but not in platelets from mice treated for 3 days or shorter, suggesting an indirect pathway. Studies with mouse bone marrow revealed that E2 replacement in ovariectomized mice reduces megakaryocyte GPVI expression. This data suggest that transdermal E2 is able to affect centrally on megakaryocyte GPVI to regulate platelet GPVI and function.
authors.affiliation: Medicine/Thrombosis Research, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Geng
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Paul F
authors.initials: PF
authors.lastname: Bray
authors.forename: Xinghong
authors.initials: X
authors.lastname: Leng
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D005260:Female; D008533:Megakaryocytes / Q000737:chemistry / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*
chemical_list: D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D004958:Estradiol