Studies in the biotransformation of cortisol to the cortoicb acids in man. I. metabolism of 21-dehydrocortisol

21-Dehydrocortisol (21-DF) is a possible intermediate in the biotransformation of cortisol (F) to the cortoic acids (21-carboxy analogues of the cortols and cortolones). 21-³H or 4-¹⁴C-labeled 21-DF was given iv to 3 normal subjects and 2 ill patients, simultaneously with F tracers labeled with the other isotope. Urinary recovery of radioactivity from 21-DF was 66-80% of that from F; 15-19% of the³H from 21-DF appeared in body water. There was significant reduction of 21-DF to F (5-8% in normal subjects and 18-19% in ill patients) but the major metabolite of 21-DF was "cortienic acid" (11β, 17α-dihydroxy-17β-carboxyandrost-4-en-3-one) which is formed only in trace amounts from cortisol. Transformation of 21-DF to the cortoic acids was small (2-6%), about ⅓ as great as transformation of cortisol. The isotope ratios (isotope from 21-DF/isotope from F) of various urinary metabolites were measured and compared with those of THF, THE and F, which were the same and were set equal to 1.00. The degree to which the ratio of any metabolite exceeds 1.00 is a measure of the degree to which 21-DF is a better precursor for it than F, by pathways not going through F. The following metabolites were "enriched" with respect to 21-DF: cortol (3.1-6.9), cortolone (2.6-3.8), cortolic acid (2.8) and β-cortolic acid (7.2). Cortolonic acid and β-cortolonic acid showed no enrichment. It was concluded that 21-DF is not a precursor of the cortolonic acids, and though it can be a precursor of the cortolic acids, it is not a normal intermediate in the cortisol → cortolic acids pathway because its transformation to the cortolic acids is many times less than that of cortisol, and its major metabolite, cortienic acid, is an insignificant metabolite of cortisol.