common precursor of testosterone (T) and dihydrotestosterone (DHT). We reported 5a-androstane-3b,17b-diol (3b-diol), which is inactive androgen metabolized from DHT, can be converted back to DHEA and finally to DHT. In this pathway, 3b-hydroxysteroid dehydrogenase (3bHSD) is the key enzyme for the conversion from DHEA and epiandrosterone (epiAND) to DHT, and Rui et al. reported abiraterone inhibited 3b-HSD in CRPC. We examined the effect of CYP17 inhibitors on the intracrine back-conversion pathway induced by 3b-diol in prostate cancer cells. METHODS: LNCaP cells were incubated in the presence of 3bdiol or DHEA 10nmol/L with or without CYP17 inhibitors (abiraterone, ketoconazole, or orteronel) 10nmol/L. In all experiments, LNCaP cells were incubated without any androgens and CYP17 inhibitors as a control (CTRL). After incubation, PSA levels in the media were determined by enzyme immunoassay, and androgen levels in media were measured by LC-MS/MS. RESULTS: By adding DHEA or 3b-diol in media, PSA levels were increased (p 1⁄4 0.013 and p < 0.001, respectively). 3b-diol highly activated AR about five-times compared to DHEA. Inhibition of PSA secretion by abiraterone, ketoconazole and orteronel was found in the presence of DHEA (p < 0.001, p 1⁄4 0.002, and p 1⁄4 0.017, respectively). 3b-diol-induced PSA accumulation in media was inhibited by abiraterone, not ketoconazole or orteronel. By adding 3b-diol in medium, DHEA, androstenediol (A-diol), androstendione (A-dione), T, and DHT levels were increased compared to CTRL. In the media with 3b-diol and abiraterone, A-dione, T, DHT, and 5a-androstanedione (5a-A-dione) levels were decreased, DHEA, 5-diol, and epiAND levels increased compared to 3b-diol only. CONCLUSIONS: AR was highly activated by 3b-diol compared to DHEA through the conversion of 3b-diol to DHT by way of epiAND and 5a-A-dione, which abiraterone blocked by inhibiting 3b-HSD. Abiraterone has a potential to inhibit the intracrine back-conversion pathway.