Androgen-mediated sensitivity in platelet aggregation.
Platelet responsiveness to an aggregating stimulus (ADP) was greater (X10) in male than in female rats. Castration reduced aggregability in males (X4) and increased it in females (X3). Pretreatment with testosterone (1 mg/kg, sc) enhanced platelet aggregability in both sexes and restored the diminished responsivity observed in castrated males. Incubation of platelets with testosterone (1-10 ng/ml) potentiated rat (18.0 +/- 1.5%) and guinea pig (40.0 +/- 5.0%) aggregability when compared with vehicle-treated platelets. Estradiol (1 mg/kg, sc) in vivo or estradiol, progesterone, and deoxycorticosterone (1 microng/ml) in vitro had the opposite effect and decreased aggregability. The rank order of effectiveness of androgens in vitro was dihydrotestosterone, testosterone, methyltestosterone, androstendione, and androsterone, which correlates with their androgenicity. The effect of androgens was antagonized in vitro by the antiandrogen (Flutamide) and by estradiol. These data suggest that gonadal steroids may play a role in regulating platelet function in the rat and guinea pig.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors
D000728:Androgens; D013739:Testosterone; D003900:Desoxycorticosterone; D011374:Progesterone; D004958:Estradiol; D000244:Adenosine Diphosphate; D005485:Flutamide