Differential hydroxylations of estrone and estradiol in man.
We sought to test the hypothesis that in man, the fraction of estradiol (E2) that does not undergo oxidation to estrone (E1) in vivo is not available for subsequent hydroxylation at C-2 and C-16 alpha. Using radiometric methods, the extent of 17-oxidation of E2, 2-hydroxylation of E2 and E1, and 16 alpha-hydroxylation of E2 and E1 was determined in normal men. It was expected that administered E1 would transfer more of the tritium from C-2 and C-16 alpha into body water than would the corresponding dose of E2 and that the difference would be related to the fraction of E2 not oxidized at C-17. In eight of eight paired studies, the generation of tritiated water was substantially greater from [2-3H]E1 than from [2-3H]E2. By contrast, in six of seven paired studies, it was the administered [16 alpha-3H]E2 rather than [16 alpha-3H]E1 that underwent greater hydroxylation. No consistent relationship was found between the extent of 17-oxidation and the subsequent hydroxylation. We had previously hypothesized that the differences in the oxidative metabolism of E2 between men and women was due primarily to the lesser conversion of E2 to E1 in men and that the lesser extents of the subsequent hydroxylations at C-2 and C-16 alpha were secondary to this initial difference. The present work indicates that while this concept may be valid in reference to the decreased 2-hydroxylation in men, it does not account for the lesser extent of 16 alpha-hydroxylation.
D000328:Adult; D001711:Biotransformation; D004958:Estradiol / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D039181:Steroid 16-alpha-Hydroxylase; D014316:Tritium
D014316:Tritium; D004970:Estrone; D004958:Estradiol; D039181:Steroid 16-alpha-Hydroxylase