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-Estradiol, Conjugated Equine Estrogen and Raloxifene on mRNA Expression, Aggregation and Secretion in Platelets
1 Department of Physiology and Bioengineering, Mayo Clinic College of Medicine, Rochester, MN, USA
2 Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
3 Section of Hematology Research, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Department of Physiology and Bioengineering, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
* To whom correspondence should be addressed. E-mail: miller.virginia{at}mayo.edu.
Changes in platelet functions could contribute to thrombotic risk associated with estrogen treatments. This study was designed to test the hypothesis that three clinically relevant estrogenic treatments affect platelet function comparably. Adult female pigs were ovariectomized and randomized to either no treatment or treatment with oral 17
-estradiol (2 mg/day); conjugated equine estrogen (CEE, 0.625 mg/day) or raloxifene (60 mg/day) for four weeks. Platelet turnover, aggregation and secretion were assessed prior to and after treatment. Platelet turnover and mRNA increased significantly only in pigs treated with 17-estradiol. Expression of estrogen receptors increased with ovariectomy and decreased with all treatments. Platelet aggregation and secretion of ATP, platelet-derived growth factor and matrix metalloproteinase-2 increased with ovariectomy. All treatments reduced both aggregation and secretion. Expression of mRNA for constitutive nitric oxide synthase protein (eNOS) but not eNOS protein increased with ovariectomy. Only eNOS mRNA decreased with all treatments but only treatment with 17-estradiol increased secretion of nitric oxide from intact platelets. Platelets from 17-estradiol treated-animals caused relaxation of coronary arteries, which was sensitive to inhibition of nitric oxide. Although three different estrogenic treatments reversed increases in platelet aggregation caused by ovariectomy, only 17-estradiol increased platelet RNA and release of platelet-derived nitric oxide. These differences reflect transcriptional and post-transcriptional regulation of protein synthesis in bone marrow megakaryocytes and circulating platelets.
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