Metabolism and conjugation of cortisol by various dog tissues in vitro

The metabolism and conjugation in vitro of [4-¹⁴C]-cortisol by a variety of dog tissues have been investigated. Quantitatively, oxidation at C-11 to cortisone was the major biotransformation which occurred in all tissues studied. Reduction of C-20, primarily to 20β-dihydro metabolites and side chain cleavage to C-19 steroids was also demonstrated to an appreciable extent in all the tissues except the brain. Of the extrahepatic tissues, the kidney and adrenal cortex were the most metabolically active. Reduction of the 4–5 double bond and C-3 ketone of ring A was characteristic of the liver. 5β-Isomers were the major type of products. Small quantities of 6β-hydroxycortisol and 6β-hydroxycortisone were synthesized by the adrenal cortex and the liver. Of special interest was the isolation of 6β-hydroxy-20β-dihydro derivatives from the liver. A small fraction of ring A-reduced metabolites was conjugated with glucuronic acid in the liver, while the capacity to sulfate cortisol was noticed in the adrenal, liver, kidney, muscle and lung.