Biotransformations of the C-20-dihydro metabolites of cortisol in man

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 l l a 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 β-cortol) and most of the R-U metabolites retained the 11-keto group (major metabolite β-cortolone); 2) the "setpoint" 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.