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.
Bélanger
A
A
MRC Group in Molecular Endocrinology, CHUL Research Center, Ste-Foy, Québec, Canada.
Brochu
M
M
Lacoste
D
D
Noël
C
C
Labrie
F
F
Dupont
A
A
Cusan
L
L
Caron
S
S
Couture
J
J
D000293:Adolescent; D000328:Adult; D000375:Aging; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives* / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003687:Dehydroepiandrosterone / Q000378:metabolism; D005965:Glucuronates / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013431:Sulfates; D014407:Tumor Cells, Cultured
D005965:Glucuronates; D012738:Sex Hormone-Binding Globulin; D013431:Sulfates; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D000735:Androstenedione; D003687:Dehydroepiandrosterone