STEROID GLUCURONIDES - HUMAN CIRCULATORY LEVELS AND FORMATION BY LNCAP CELLS

We studied the relationship between circulating androsterone glucuronide, androstane-3-alpha,17-beta-diol glucuronide and androstane-3-beta,17-beta-diol glucuronide concentrations and adrenal as well as testicular C-19 steroids in men. Among the three 5-alpha-reduced steroid glucuronides, androsterone glucuronide is the predominant C- 19 steroid glucuronide measured in plasma and its levels are markedly elevated compared to those of the non-conjugated steroid. The marked rise in testosterone during puberty was strongly correlated with the increase in both androsterone glucuronide and androstane-3-alpha, 17-beta-diol glucuronide, thus suggesting that testicular C-19 steroids are the main precursors of the steroid glucuronides. We also found that the presence of testicular androgen in plasma contributes to approx. 70% of plasma androsterone glucuronide and androstane-3-alpha, 17-beta-diol glucuronide. Our data suggest that the adrenal C-19 steroids remaining in circulation after castration in men are converted into potent androgen which are then glucuronidated by UDP-glucuronyltransferase. We also demonstrated that the human prostate cell line LNCaP is capable of converting to a large extent androstenedione into androsterone glucuronide. Our data further confirm that glucuronidation is a major pathway of steroid metabolism in steroid target tissues.