Characterization of 17B-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate

In the present study, expressions of 17B-hydroxysteroid dehydrogenase (17HSD) types 1, 2 and 3, 5α-reductase type 2 and human androgen receptor mRNAs were determined in 12 benign prostatic hyperplasia and 17 prostatic carcinoma specimens. 17HSD type 2 was found to be the principal isoenzyme expressed in the prostate. Significantly higher expressions of 17HSD type 2 and 5α-reductase type 2 were detected in benign prostatic hyperplasia compared with the carcinoma specimens. Expression of the androgen receptor in the 2 groups was not significantly different. 17HSD type 3 mRNA was not detected in any of the specimens investigated. Only low constitutive expression of the 2.3 kb mRNA of 17HSD type I was seen. Immunohistochemical analyses indicated that this did not lead to significant enzyme expression, only faint staining for the enzyme protein being detected, mainly in uroepithelial cells. No significant correlation was found between any of the mRNAs analyzed, but the data on 5α-reductase type 2 mRNA support the presence of an increased proportion of 5α-dihydrotesterone in the hyperplastic prostate. In cultured PC-3 prostatic cancer cells and in transiently transfected human embryonic kidney 293 cells, 17HSD type 2 was found exclusively to convert 5α-dihydrotestosterone and testosterone into the less potent 17-keto compounds 5α-androstanedione and 4-androstenedione, respectively. We suggest that the 17HSD type 2 isoenzyme plays a part in the metabolic pathway, resulting in the inactivation of testosterone and 5α-dihydrotestosterone locally in the prostate. The enzyme expressed in the prostate could, therefore, protect cells from excessive androgen action. © 1996 Wiley-Liss, Inc.