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 platel et calcium levels are affected by exogenous hormones, intracellular ca lcium and release were studied in platelets in various hormonal enviro nments and findings were correlated with platelet adhesion and aggrega tion. Platelet intracellular calcium concentration and release was sig nificantly decreased in women ingesting tamoxifen compared to controls and significantly increased, as was platelet adhesion, in oral contra ceptive users. Platelets incubated ex vivo with estradiol had increase d intracellular calcium and release but there was decreased adhesion t o fibronectin. Intracellular calcium concentration and release were no t affected when platelets were incubated with tamoxifen. Adhesion to c ollagen III was increased in tamoxifen-incubated platelets. Only oral contraceptive users had increased sensitivity to aggregating agents. T his 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 t o the degree of platelet adhesion and aggregation in vivo.