In situ androgen producing enzymes in human prostate cancer

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5 alpha-reductase types 1 and 2, and 17 beta-hydroxysteroid dehydrogenase type 5 (17 beta-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n = 70 ), and correlated the findings with clinicopathological features of the patients. 17 beta-HSD5 immunoreactivity was detected in 54 cases (77%), 5 alpha-reductase type 1 in 51 cases (73%) and 5 alpha-reductase type 2 in 39 cases (56%). 5a-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17 beta-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5 alpha-reductase type 1 and type 2, and 17 beta-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.