Epithelial- Stromal Interactions in the Regulation of Rat Ventral Prostate Function: Identification and Characterization of Pathways for Androgen Metabolism in Isolated Cell Types*

Abstract

Androgen metabolism plays a significant role in the androgen regulation of prostate cell function. In this report the various pathways for androgen metabolism in primary cultures of rat ventral prostate epithelial and stromal cells were identified and characterized by in vitro whole cell assays, using HPLC. Confluent cultures of both cell types were incubated with supraphysiological concentrations (50 nM) of tritiated androgens (testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha(and 3 beta), 17 beta-diols, and delta 4-androstene-3,17-dione), and the metabolites were analyzed at several time points over a 24-h period. The metabolism studies indicated that 5 alpha-reductase activity, the oxidative reactions of 3 alpha-, 3 beta-, and 17 beta-hydroxysteroid oxidoreductases, and the reductive reaction of 3 beta-hydroxysteroid oxidoreductase were expressed at significantly higher levels in epithelial cells compared to stromal cells. The reductive reactions of 3 alpha- and 17 beta-hydroxysteroid oxidoreductases were similar in both cell types. In contrast, stromal cells exhibited substantially higher levels of 6 alpha/7 alpha-hydroxylase activity. In addition, stromal cells were capable of metabolizing 5 alpha-dihydrotestosterone directly to a new unidentified polar androgen metabolite (HO5 alpha-DHT). Overall, epithelial cells were approximately 29 times more capable than stromal cells of forming the biologically active androgen 5 alpha-dihydrotestosterone. Conversely, stromal cells were more capable of forming biologically inactive polar androgen metabolites.