Metabolism of androstenedione by human platelets: a source of potent androgens

The metabolism of tritium-labeled androstenedione by human platelets was studied in vitro. The following metabolites were identified: testosterone, 5 alpha-androstane-3,17-dione, androsterone, isoandrosterone, 5 alpha-dihydrotestosterone, and 5 alpha-androstane-3 alpha,17 beta-diol. The rates of formation of these metabolites remained linear with time of incubation up to 2 h and with increased platelet protein concentration up to 14.6 mg/ml. Estrogens and 5 beta-reduced metabolites were not formed by platelets. The major enzyme systems involved in the metabolism of androstenedione in human platelets were the 17 beta-hydroxysteroid oxidoreductase and 5 alpha-reductase activities; in addition, 3 alpha-and 3 beta-hydroxysteroid oxidoreductase activities were also present in these megakaryocyte fragments. Thus, it appears that platelets are a potential site of extraglandular conversion of androstenedione to potent androgens in man. It is also possible that androgens formed within the platelet may affect platelet function by regulating their sensitivity to aggregating stimuli.