Human prostatic cells in culture: different testosterone metabolic profile in epithelial cells and fibroblasts from...

The prostate gland depends on androgens for its development and the maintainance of its differentiated structures and secretory function. We have characterized the metabolic pathways of testosterone in isolated epithelial (NE) and fibroblast cultured cells from normal (NF) and hyperplastic (BPHF) prostates, in order to provide a tool for the study of androgen function in the prostate in defined conditions. In NE, 5 alpha-reductase (5 alpha-R) is the predominant metabolic pathway whereas in NF 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSDHase) is the main activity. However, 5 alpha-R in NF is 5-10-fold higher than in NE. Furthermore, a striking increase in both enzyme activities is observed in fibroblasts from hyperplastic prostates (5 alpha-R x 8; 17 beta-OHSDHase x 250 relative to NF). delta 4-androstenedione could serve as a reservoir for testosterone or could be a tentative protective mechanism directing testosterone metabolism towards an inactive molecule. In conclusion, human epithelial and stromal cells maintain in culture their main metabolic characteristics. The knowledge derived from these studies should facilitate the reconstitution and analysis of their interactions, which in vivo may modify their respective metabolism.