Radiometric analysis of biological oxidations in man: sex differences in estradiol metabolism.

The oxidative metabolism of estradiol was studied in normal men and women by a radiometric procedure that provides information on the totality of the biotransformations concerned. The release of 3H into body water from estradiol labeled with 3H in the 17 alpha, 16 alpha, and C-2 positions permits measurement of the rate and extent of 17 beta-ol oxidation and of the competing hydroxylations at C-2 and 16 alpha, which lead to products with different biologicaly properties. In both men and women the 17 beta-ol oxidation is the most rapid transformation, followed by 2-hydroxylation and finally by 16 alpha-hydroxylation. Hydroxylation at C-2 predominates by a faccto of 2-4 over 16 alpha-hydroxylation. In men a large fraction (37%) of the substrate is unmetabolized at any of the three sites and is not excreted in urine; in women the corresponding fraction is only 18%. The estradiol fraction that does undergo metabolism is hydroxylated at C-2 vs. 16 alpha to a greater extent in women than in men. These major sex differences in the metabolism of estradiol in the human may have an important influence on the expression of the biological actions of the hormone. The radiometric technique used in this study can be generally applied to study the oxidative transformations of hormones, drugs, and other exogenous chemical that can be specifically labeled at reactive sites.