Estradiol Is Concentrated in Human Platelets and Is Released upon Activation.

Abstract

Background and Aim: Estrogens are prothrombotic in both normal and atherosclerotic vessels. There is evidence that exogenous estrogen modifies platelet reactivity and signaling pathways, but very little is known about sex hormone metabolism in platelets or whether platelet estrogen stores contribute to atherothrombosis. To begin to characterize the role of sex hormones in platelet biology, we measured estradiol (E2), estrone (E1) and testosterone (T) concentrations within platelets and plasma of normal healthy men and women. Additionally, we tested the hypothesis that platelets have the capacity to release E2 during thrombin-stimulated platelet aggregation and activation.Methods and Results: Platelets and plasma were prepared from platelet-rich plasma (PRP) samples of 16 male (age 24–63), 13 premenopausal female (age 25–34) and 8 menopausal female (age 39–65) donors; no females were using exogenous hormones. E2, E1 and T were determined by Gas Chromatography-Mass Spectrometry. Hormone content in platelets and plasma was expressed per mL of PRP. Plasma E2, E1 and T levels were within the range of values previously reported in the literature. E2 concentrations were significantly higher in platelets compared to plasma in men (p<0.01) but not in women (premenopausal p=0.33; menopausal p=0.16). The geometric mean and 95% CI for platelet and plasma E2 levels were 199 (114–349) and 55 (37–81) pM for men, 360 (154–831) and 235 (158–357) pM for premenopausal women, and 107 (52–224) and 40 (15–118) pM for menopausal women, respectively. Conversely, T concentrations were significantly lower in platelets than in plasma in both men and women (p<0.01). E1 levels in platelets and plasma were not significantly different within men and within women. In a subset of participants, PRP samples were incubated with 0.5 U/mL thrombin for 10 minutes at 37oC and estradiol levels were measured in the non-clotted plasma+platelet releasate. Compared to no thrombin, thrombin-treated PRP from male subjects (n=7) yielded a 1.6 to 6.7 fold increase in E2 levels (p<0.01). The incubation of PRP from premenopausal (n=5) and menopausal women (n=4) with thrombin did not produce a significant change in E2 release.Conclusion: Our results show that platelets have the capacity to concentrate E2 and may serve as a vascular vehicle for the delivery of this prothrombotic factor upon platelet activation.