Tetrahydrocortisol metabolism in man

Abstract

Tetrahydrocortisol (THF) metabolism was studied by I.V. administration of trace amounts of 3H-THF to 3 normal men and 4 patients with miscellaneous illnesses. The principal urinary steroid was THF. This constituted about half of the “glucosiduronates” in the normal subjects, but significantly more (61–79%) in 3 of the 4 patients. Reduction of the 20-ketone of THF was quantitatively less prominent than the corresponding reaction for THE, but similarly stereoselective. Total cortols constituted 2–12% of the “glucosiduronates”, and the 111β-epimer predominated by about 15:1. The major conversion product of THF was 11β-hydroxyetiocholanolone, 12–25% of the “glucosiduronates” in normal subjects. Three of the four patients showed significantly diminished formation of this metabolite (3–5% of the “gluco-siduronate”). This suggests that diminished side-chain removal of THF may occur non-specifically in ill subjects. In one of these 3 patients, the low 11β-hydroxy-etiocholanolone formation was associated with extremely high β-cortol formation (32% of the “glucosiduronate” suggesting that β-cortol serves as one of the immediate precursors of 11β-hydroxyetiocholanolone.