CORTISOL METABOLISM IN MAN: OBSERVATIONS OF PATHWAYS, POOL SIZES OF METABOLITES AND RATES OF FORMATION OF METABOLITES*

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Abstract
The specific activities of several cortisol metabolites were evaluated in urine samples collected every 15 minutes from normal adult volunteers after the rapid intravenous administration of trace amounts of cortisol-4-C14. The compounds evaluated were cortolone, tetrahydrocortisol (THF), allotetrahydrocortisol (allo-THF), tetrahydrocortisone (THE) and cortisol (F). During the course of the experiments small quantities of nonlabeled metabolites were administered intravenously. By isotope dilution, it was found that 2 of the major metabolites of F, THF and THE, are derived mainly from F and cortisone respectively. There is little interconversion of the 2 metabolites, THF and THE. A fall in cortolone specific activity after the addition of unlabeled THF and THE suggests that these compounds may be, to a small extent, precursors of cortolone. "Readily miscible" pool sizes of metabolites were calculated by isotope dilution and the relative sizes of the pools thus calculated were found to be proportional to the relative amounts of metabolites excreted as glucuronosides. In 2 studies performed during adrenocorticotropin administration, the "rates of formation" (mg/24 hr.) of THF, allo-THF and THE accounted for approximately 80% of the total turnover of F.

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