Metabolism of androstenedione by guinea-pig peritoneal macrophages: synthesis of testosterone and 5 alpha-reduced metabolites

Abstract

Androstenedione metabolizing enzymes present in guinea-pig peritoneal macrophages were investigated using tritium-labeled androstenedione as the substrate. We found that the metabolites of [3H]-androstenedione produced by these macrophages were testosterone, 5 alpha-androstane-3,17-dione, isoandrosterone, androsterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol. The rates of metabolite formation remained linear as a function of time of incubation for approximately 30 min and with macrophage number up to 2 x 10(7) cells per ml. The formation of these metabolites in indicative that the following androstenedione metabolizing enzymes are present in guinea-pig peritoneal macrophages: 5 alpha-reductase, 3 alpha-hydroxysteroid oxidoreductase, 3 beta-hydroxysteroid oxidoreductase and 17 beta-hydroxysteroid oxidoreductase. It is possible, therefore, that the macrophage, in vivo, may play a role in the metabolism of blood-borne androstenedione to potent androgens. These hormones are important in the regulation of many biological processes, possibly including the activity of the macrophage itself.