DISTINCT ANDROGEN 5-ALPHA-REDUCTION PATHWAYS IN CULTURED FIBROBLASTS AND IMMORTALIZED EPITHELIAL-CELLS FROM NORMAL HUMAN ADULT PROSTATE

All androgen-sensitive peripheral tissues and cells, including the pro state, are commonly believed to possess the ability to metabolize test osterone. We report on the in vitro metabolism of tritiated testostero ne performed in immortalized human adult normal prostatic epithelial c ells and in human adult normal prostate fibroblastic cells (stromal ce lls). These two cell types were incubated separately with increasing t estosterone concentrations (1 to 50 nM.) for 2 and 4 hours, after whic h the testosterone metabolic profile was analyzed. Data analysis provi ded evidence, for the first time, of the existence of two different 5 alpha-reduced metabolic pathways. Stromal cells preferred the androste rone pathway via the oxidative androstenedione formation, whereas epit helial cells preferred the reductive 5 alpha-dihydrotestosterone pathw ay. These two 5 alpha-reduced metabolites were produced in nearly equa l quantities regardless of testosterone concentration or time of incub ation. Since interactions between epithelial and stromal cells are inv olved in the development of the prostate, the availability of defined epithelial and stromal cells suitable for in vitro experiments provide s a useful tool for the study of the contribution of androgens to thes e interactions. The model presented in this study would permit a bette r evaluation of the intraprostatic regulation of androgen metabolism a nd the contribution of the anti-5 alpha-reductase drugs to the managem ent of benign prostate hyperplasia.