DIFFERENT CONVERSION METABOLIC RATES OF TESTOSTERONE ARE ASSOCIATED TO HORMONE-SENSITIVE STATUS AND HORMONE-RESPONSE OF HUMAN PROSTATE-CANCER CELLS

The main goal of the present work was to compare the ability of human prostate cancer (PCa) cells to metabolize testosterone (T) in living c onditions. To this end we studied three different human PCa cell lines (LNCaP, DU145 and PC3) having different hormone-sensitive status and capability of response to androgens. We used an original approach whic h allows the evaluation of conversion metabolic rates in growing cells after administration of labeled steroid precursor (presently T), at p hysiological concentrations (1-10 nM). Analysis of both precursor degr adation and formation of several products was carried out using revers e phase-high performance liquid chromatography (RP-HPLC) and ''on line '' radioactive detection. Comparison of the three human PCa cells reve aled that their metabolic aptitude differed in many respect: (i) rates of precursor degradation, (ii) different products' formation, and (ii i) extent of conjugate production. In detail, PC3 cells quickly degrad ed T and exhibited high formation rates of androstenedione (A-4-ene-Ad ); both DU145 and LNCaP cells mostly retained high levels of unconvert ed T, with a limited production of A-4-ene-Ad and its 17-keto derivati ves (if any). Either LNCaP or DU145 cells generated a relatively high amount of dihydrotestosterone (DHT). In contrast, neither DHT nor its main metabolites were detected in PC3 cells at both short and longer i ncubation times. As expected, T degradation and A-4-ene-Ad production were highly correlated (r = 0.97; P < 0.03); similarly, A-4-ene-Ad and DHT formation showed a negative, significant correlation. Negligible production of conjugates was noted in both PC3 and DU145 cells, whilst it was remarkable in LNCaP cells (ranging from 43 to 57%). Overall, o ut data indicate that human PCa cells degrade T quite differently, fav oring alternatively reductive or oxidative patterns of androgen metabo lism.