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.