A NOVEL COCULTURE MODEL FOR BENIGN PROSTATIC HYPERPLASIA EXPRESSING BOTH ISOFORMS OF 5-ALPHA-REDUCTASE

We have developed a coculture system for primary fibroblast and epithe lial cells derived from benign prostatic hyperplasia (BPH) that retain ed many of the characteristics of the intact human prostate. In contra st to separately cultured prostate fibroblast and epithelial cells, co cultures of fibroblasts and epithelial cells maintained messenger ribo nucleic acid expression and functional activity for both isoenzymes of 5 alpha-reductase (type I and type II) as well as maintained expressi on of androgen receptors and prostate-specific antigen. Furthermore, l evels of prostate-specific antigen secreted by cocultured epithelial c ells were increased by treatment with androgens, mimicking the situati on in the human gland. This contrasted with conventionally cultured fi broblasts or epithelial cells, which failed to express 5 alpha-reducta se type II and rapidly lost expression of androgen receptors and andro gen sensitivity upon being placed into culture. Electron microscopy de monstrated intracellular structures indicative of the differentiated s tate of the cocultured cell types, including round nuclei, tonofibrils , and microvilli in epithelial cells and elongated nuclei; large amoun ts of Golgi and cilia; along with immature collagen fibers in fibrobla sts. The present study demonstrates that the coculture model reflects more closely the in vivo system for human BPH and is thus a far more s uitable model for investigating the molecular and cellular events that underlie BPH than current in vitro systems.