Androgen 5α-reductase and 3α-hydroxysteroid dehydrogenase activities in ventral prostate epithelial and stromal cells from immature and mature rats

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Abstract
To study androgen-mediated differentiation in the rat ventral prostate, we separated the two principal cell types (epithelial and stromal) derived from prostates of immature and mature rats on two continuous Percoll gradients. Cells were immediately placed in culture medium. Testosterone metabolism by the two prostatic cell types was evaluated using [3H]testosterone and quantifying the formation of 5α-[3H]dihydrotestosterone (5α-DHT) and 5α-[3H]androstane-(3α or 3β), 17β-diols. In epithelial cells from both immature and mature rat prostates the major testosterone metabolites were 5α-DHT and 5α-androstane-3α, 17β-diol. Stromal cells metabolized less testosterone than did the epithelial cells. Differences in the relative levels of the various metabolites were observed for the two age groups. To examine in more detail the changes in testosterone metabolism observed in vitro both types of cells and unfractionated cells from immature and mature rat prostates were assayed for testosterone 5α-reductase (using testosterone as substrate) and 3α-hydroxysteroid dehydrogenase (using 5α-DHT as substrate) activities (expressed as pmol substrate reduced/min per 106 cells). In immature rats both 5α-reductase and 3α-hydroxysteroid dehydrogenase activities were localized in the epithelial cell fraction (17 and 52 respectively); stromal cells showed lower 5α-reductase and 3α-hydroxysteroid dehydrogenase activity (4 and 4). Relative to epithelial cells from immature rats epithelial cells from mature rats showed a decrease in 5α-reductase (7) and an increase in 3α-hydroxysteroid dehydrogenase (160) activity while stromal 5α-reductase showed little change (3) and 3α-hydroxysteroid dehydrogenase increased to 22. Because there are more epithelial than stromal cells in the rat prostate, the former can be considered important sites for 5α-reductase and 3α-hydroxysteroid dehydrogenase activities. This contrasts with the human prostate where there is more 5α-reductase activity in the stroma than in the epithelium.