Conversion of androstenedione to testosterone and other androgens in guinea-pig alveolar macrophages.

Alveolar macrophages obtained by bronchoalveolar lavage of lungs of male and female guinea pigs were incubated with tritium-labelled androstenedione to evaluate the steroid metabolizing enzymes in these cells. The radiolabeled metabolites were isolated and thereafter characterized as testosterone, 5 alpha-androstanedione, 5 alpha-dihydrotestosterone, androsterone, isoandrosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol. Thus, the following androstenedione metabolizing enzymes are present in guinea-pig alveolar macrophages: 17 beta-hydroxysteroid dehydrogenase, 5 alpha-reductase, 3 beta-hydroxysteroid dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase. The predominant androstenedione metabolizing enzyme activity present in alveolar macrophages was 17 beta-hydroxysteroid dehydrogenase. The rate of testosterone formation increased with incubation time up to 4 h, and with macrophage number up to 1.6 X 10(7) cells per ml. Androstenedione metabolism was similar in alveolar macrophages obtained both from male and female guinea pigs. These results suggest that alveolar macrophages may be a site of peripheral transformation of blood-borne androstenedione to biologically potent androgens in vivo and, therefore, these cells may contribute to the plasma levels of testosterone in the guinea pig.

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.

Androstenedione metabolism by human lymphocytes.

Intact human lymphocytes were incubated with tritium-labeled androstenedione; after extraction and appropriate chromatographic separation, followed by crystallization to constant tritium to carbon-14 ratio to establish radiochemical homogeneity, the following metabolites were identified: testosterone, 5 alpha-androstane-3,17-dione, 5 alpha-dihydrotestosterone, androsterone and isoandrosterone. Neither estrogen nor 5 beta-reduced metabolites were found as products. The major androstenedione metabolizing activities in human lymphocytes were 5 alpha-reductase and 17 beta-hydroxysteroid oxidoreductase; in addition, 3 alpha-and 3 beta-hydroxysteroid oxidoreductase activities also were present in these cells. The rates of metabolite formation were linear with incubation time up to 4 h, and with cell number up to 2 x 10(7) lymphocytes per ml for the 5 alpha-reduced products and up to 1.6 x 10(7) lymphocytes per ml for testosterone. These findings are suggestive that, in the human, lymphocytes are a potential site of peripheral metabolism of androstenedione to potent adnrogens.