title: Inhibition of oxidative-stress-induced platelet aggregation by androgen at physiological levels via its receptor is associated with the reduction of thromboxane A2 release from platelets.
abstract: BACKGROUND
  Platelets play a crucial role in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of our study are to assess the effect of androgen at physiological concentration via its receptor on oxidative-stress-induced platelet aggregation and to further elucidate the possible mechanism.
  
  
  RESULTS
  Plasma dihydrotestosterone (DHT) was determined by ELISA using a commercially available kit. Platelet aggregometer was used to measure platelet aggregation. The contents of thromboxane B(2) (TXB(2)) were assayed with radio-immunoassay. Our results showed that addition of DHT (2 nM) significantly inhibited platelet aggregation induced by hydrogen peroxide (H(2)O(2)) (10 mM, 25 mM) in PRP diluted with Tyrode's buffer. Moreover, H(2)O(2)-induced platelet aggregation decreased in sham-operated rats. However, H(2)O(2)-induced platelet aggregation significantly increased in castrated rats. Replacement of DHT inhibited H(2)O(2)-induced platelet aggregation in castrated rats. After PRP was pretreated with flutamide, H(2)O(2)-induced platelet aggregation increased in castrated rats again. Presence of DHT (2 nM) obviously inhibited H(2)O(2)-induced thromboxane A(2) (TXA(2)) release in castrated rats. Pretreatment of DHT and flutamide increased H(2)O(2)-stimulated TXA(2) release from platelet in castrated rats again. Castration caused a significant reduction in plasma testosterone and DHT levels, whereas DHT replaced at a dose of 0.25 mg/rat restored the circulating DHT to physiological levels, without being altered by treatment with flutamide. The plasma TXB(2) increased in castrated rats as compared with that in sham-operated rats. Replacement with DHT reduced plasma TXB(2) contents in castrated rats. However, flutamide supplementation increased plasma contents of TXB(2) in castrated rats again.
  
  
  CONCLUSIONS
  Androgen at physiological doses via its receptor inhibits oxidative-stress-induced platelet aggregation, which is associated with the reduction of TXA(2) release from platelets.
authors.affiliation: Division of Geriatric Cardiology, Chinese PLA General Hospital at No. 28, Fuxing Road, Beijing 100853, PR China. lishijun817@126.com
authors.forename: ShiJun
authors.initials: S
authors.lastname: Li
authors.forename: XiaoYing
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Xinli
authors.initials: X
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000097:blood / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood / Q000378:metabolism*