Androstenedione metabolism in human alveolar macrophages

The metabolism of [3H]androstenedione by human alveolar macrophages was investigated. Alveolar macrophages were obtained by bronchopulmonary lavage by use of a heparinized saline solution devoid of Ca++ and Mg++. After purification, the macrophages were incubated at 37 C in RPMI-1640 medium that contained glucose and [1,2,6,7-3H]androstenedione under various experimental conditions. Control incubations were conducted without macrophages. After incubation, 14C-labeled steroids that corresponded to the metabolites were added as internal recovery standards. The metabolites were characterized by chromatography and crystallization to constant 3H to 14C ratios. Human alveolar macrophages convert [3H]androstenedione to 5 alpha-androstane-3,17-dione, testosterone, 5 alpha-dihydrotestosterone, androsterone, and isoandrosterone. Unidentified polar metabolites also were formed. Therefore, the following enzymes are present in these cells: 5 alpha-reductase, 17 beta-hydroxysteroid dehydrogenase, 3 alpha-hydroxysteroid dehydrogenase, 3 beta-hydroxysteroid dehydrogenase, and unknown hydroxylase(s). The rates of formation of the principal metabolites, 5 alpha-androstanedione and testosterone, remained linear up to 4 h of incubation and with macrophage number up to 1.5 X 10(7) cells/ml. These findings suggest that alveolar macrophages may be involved in the peripheral metabolism of androstenedione to potent androgens in man. It is possible that androgens, formed from blood-borne androstenedione within alveolar macrophages, may modulate phagocytic and other activities in these cells.