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H. LEON BRADLOW, BARNETT ZUMOFF, DAVID K. FUKUSHIMA, LEON HELLMAN, T. F. GALLAGHER, Biotransformations of the C-20-Dihydro Metabolites of Cortisol in Man, The Journal of Clinical Endocrinology & Metabolism, Volume 34, Issue 6, 1 June 1972, Pages 997–1002, https://doi.org/10.1210/jcem-34-6-997
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Abstract
The biotransformations of the C-20-dihydro metabolites of cortisol were studied as follows: Two normal subjects received iv tracer doses of 14C-Reichstein's substance E; one of the tracers was also labeled with tritium in the 11α position. Both subjects were also studied with simultaneous tracers of 14C-Reichstein's substance E and 3H-Reichstein's substance U. One mildly ill man with diabetes mellitus, also received 14C-Reichstein's substance U. One subject with liver cirrhosis received 14C-R-E. One normal man and one mildly ill woman, with colon cancer, received 14C-Reichstein's substance epi-E; the tracer in one subject was also labeled with tritium in the 20β position.
The following findings and conclusions were reached: 1) there was considerable interconversion of Reichstein's substances E and U, but the process was slower and less complete than for cortisol and cortisone. In normal subjects, most of the R-E metabolites retained the 11-hydroxy group (major metabolite P-cortol) and most of the R-U metabolites retained the 11-keto group (major metabolite P-cortolone); 2) the “set-point” of this redox equilibrium was altered in the oxidative direction in cirrhosis (major metabolite of R-E was β-cortolone); 3) part of the 11-oxidation of R-E occurred in the kidney, as had been previously shown for cortisol; 4) oxidation of Reichstein's substance epi-E to its 11-keto metabolites (e.g., cortolone) was about 5 times as great as for R-E; and 5) in vivo oxidation of R-epi-E to cortisol did not occur to a measurable extent, similar to the previously demonstrated absence of in vivo oxidation of R-E to cortisol. Thus, the in vivo reduction of the 20-keto group of cortisol is biologically irreversible.
