Influence of hormones on platelet intracellular calcium.
The pathophysiology of thromboembolic disease associated with estrogen therapy is poorly understood. There are innumerable calcium-dependent activities involved in platelet function. To determine whether platelet calcium levels are affected by exogenous hormones, intracellular calcium and release were studied in platelets in various hormonal environments and findings were correlated with platelet adhesion and aggregation. Platelet intracellular calcium concentration and release was significantly decreased in women ingesting tamoxifen compared to controls and significantly increased, as was platelet adhesion, in oral contraceptive users. Platelets incubated ex vivo with estradiol had increased intracellular calcium and release but there was decreased adhesion to fibronectin. Intracellular calcium concentration and release were not affected when platelets were incubated with tamoxifen. Adhesion to collagen III was increased in tamoxifen-incubated platelets. Only oral contraceptive users had increased sensitivity to aggregating agents. This data suggests that 17 beta estradiol, progesterone, and tamoxifen likely have a nongenomic effect on platelet intracellular calcium and calcium release and that platelet calcium levels are closely related to the degree of platelet adhesion and aggregation in vivo.
Miller
M E
ME
Division of Hematology/Oncology, Memorial Hospital of Rhode Island, Pawtucket 02860, USA.
Thorpe
S L
SL
Dores
G M
GM
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D002118:Calcium / Q000097:blood*; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D004958:Estradiol / Q000009:adverse effects; D005260:Female; D005353:Fibronectins / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011374:Progesterone / Q000009:adverse effects; D013629:Tamoxifen / Q000009:adverse effects*
D003278:Contraceptives, Oral, Hormonal; D005353:Fibronectins; D013629:Tamoxifen; D011374:Progesterone; D004958:Estradiol; D003094:Collagen; D002118:Calcium