ANDROSTENEDIONE METABOLISM IN CULTURED HUMAN OSTEOBLAST-LIKE CELLS

Bone is a target organ of androgens. The mechanism by which these steroids exert their action within bone cells is still poorly understood. The metabolism of androstenedione, the major circulating androgen in women, was, therefore, assessed in osteoblast-like bone cells cultured from bone of 16 postmenopausal women (mean age, 69 yr; range, 56-80) and 3 elderly men (mean age, 71 yr; range, 69-73) undergoing total hip replacement. Each cell strain was incubated under standardized conditions with varying concentrations of [1,2,6,7-H-3]androstenedione (0.05-5-mu-M). In every instance 5-alpha-reduced metabolites and 17-beta-hydroxysteroids were formed. There was no correlation between the volumetric density of the resected bone and androstenedione metabolism of the corresponding cultured bone cell strains. The apparent K(m) for the 5-alpha-reductase activity (sum of androstanedione and dihydrotestosterone) of all 19 cell strains was 0.7 +/- 0.1-mu-M (mean +/- SEM), and the apparent K(m) for 17-beta-hydroxysteroid dehydrogenase (sum of testosterone and dihydrotestosterone) was 2.3 +/- 0.8-mu-M (mean +/- SEM), values similar to those reported for other androgen target organs. Our results demonstrate that human osteoblast-like cells have the capacity to transform androstenedione into the more potent biological androgens testosterone and dihydrotestosterone. Since the K(m) values of both 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase exceed the serum androstenedione concentration, the formation of testosterone and dihydrotestosterone appears to be mainly a function of substrate availability.