Steroid glucuronides: Human circulatory levels and formation by LNCaP cells |
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Authors: | Alain B langer Mich le Brochu Daniel Lacoste Caroline Noë l Fernand Labrie Andr Dupont L onello Cusan Simon Caron and Jean Couture |
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Institution: | MRC Group in Molecular Endocrinology, CHUL Research Center and Laval University, Centre Hospitalier de l'Université Laval, 2705 Blvd Laurier, Ste-Foy, Québec, Canada G1V 4G2 |
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Abstract: | We studied the relationship between circulating androsterone glucuronide, androstane-3,17β-diol glucuronide and androstane-3β,17β-diol glucuronide concentrations and adrenal as well as testicular C-19 steroids in men. Among the three 5-reduced steroid glucuronides, androsterone glucuronide is the predominant C-19 steroid 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-3,17β-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-3,17β-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. |
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