期刊
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
卷 98, 期 5, 页码 349-356出版社
OXFORD UNIV PRESS
DOI: 10.1093/qjmed/hci054
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Background: Exogenously administered testosterone upregulates platelet thromboxane A(2) (TXA(2)) receptors and increases aggregation response to thromboxane mimetics in healthy male volunteers. However, the biological impact of endogenous testosterone on platelet TXA(2) receptor expression, especially in older men at risk of coronary artery disease, is unclear. Aim: To investigate the impact of reduction in circulating testosterone on platelet TXA(2) receptor expression in older men. Design: Cross-sectional case-control study. Methods: We studied surgically and/or medically castrated men with prostate cancer (group A, n = 8, aged 71 +/- 8 years) and age-matched, uncastrated urology patients (group B, n = 7, aged 67 +/- 9 years). Plasma testosterone was measured by radioimmunoassay. Platelet TXA(2) receptor expression was assessed by radioligand binding studies using radioactive I-125-BOP. Platelet aggregation responses to TXA(2)-mimetic I-BOP, and to thrombin, were also studied. Results: Group A had significantly lower plasma testosterone than group B (16 +/- 5 ng/dl vs. 308 +/- 47 ng/dl, p < 0.001). Platelet TXA(2) receptor density (B-max) but not affinity (K-d) was lower in group A (0.50 +/- 0.12 vs. 1.01 +/- 0.17 pmol/mg protein, p = 0.03). Maximum platelet aggregation response to I-BOP (E-max), but not sensitivity (EC50) was lower in group A (53 +/- 2% vs. 63 +/- 2%, p = 0.003 ANOVA). In vitro, high concentrations of hydroxyflutamide (100 mu M) competitively inhibited U46619-induced platelet aggregation in washed platelets, without affecting the binding of I-125-BOP to platelet TXA(2) receptors. Discussion: Endogenous testosterone regulates platelet TXA(2) receptor B-max and the E-max aggregation response to thromboxane mimetic I-BOP. Blockade of androgen receptors or inhibition of testosterone production may reduce platelet aggregation responses. Preliminary evidence suggests the presence of functional androgen receptors on human platelets, which may regulate TXA(2) receptor expression.
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