QJM Advance Access published online on April 8, 2005
QJM, doi:10.1093/qjmed/hci054
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1 Departments of Pharmacology and Medicine, Division of Clinical Pharmacology, Medical University of South Carolina, Charleston, South Carolina, USA
* To whom correspondence should be addressed. Background: Exogenously administered testosterone upregulates platelet thromboxane A2 (TXA2) receptors and increases aggregation response to thromboxane mimetics in healthy male volunteers. However, the biological impact of endogenous testosterone on platelet TXA2 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 TXA2 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 TXA2 receptor expression was assessed by radioligand binding studies using radioactive 125I-BOP. Platelet aggregation responses to TXA2-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 TXA2 receptor density (Bmax) but not affinity (Kd) 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 (Emax), 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 µM) competitively inhibited U46619-induced platelet aggregation in washed platelets, without affecting the binding of 125I-BOP to platelet TXA2 receptors. Discussion: Endogenous testosterone regulates platelet TXA2 receptor Bmax and the Emax 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 TXA2 receptor expression.
Received November 22, 2004
Revised January 28, 2005
Original papers
Castration reduces platelet thromboxane A2 receptor density and aggregability
A.A.L. Ajayi, E-mail: adeajayi{at}aol.com
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