Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5α-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5α-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5αDH-steroids to search for novel products of 5α-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5α-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5α-dihydro-deoxycorticosterone (5αDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5α-steroid reductase (SRD5A1) could convert from DOC to 5αDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5αDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5αDH-DOC and other products of 5α-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration. (Cancer Sci 2010).
ASJC Scopus subject areas
- Cancer Research