Oxidation of cortisol to hydroxy acid metabolites by liver cytosol.

Cytosols (post-microsomal supernatants) prepared from rat, hamster and mouse livers oxidized cortisol to 11 beta, 17, 20-trihydroxy-3-oxo-pregn-4-en-21-oic acids. Mouse liver enzymes yielded over 90% 20 alpha-hydroxy epimer from cortisol, 21-dehydrocortisol (11 alpha, 17-dihydroxy-3,20-dioxo-pregn-4-en-21-aldehyde), and 20 alpha-isocortisol (11 alpha, 17, 20 alpha-trihydroxy-3-oxo-pregn-4-en-21-aldehyde). The 20 beta-epimer of isocortisol yielded both 20 alpha- and 20 beta-hydroxy acid. Rat and hamster liver cytosols converted, 21-dehydrocortisol and 20 alpha-isocortisol to both 20 alpha and 20 beta-hydroxy acids, with the former predominant. The hamster enzyme oxidized 20 beta-isocortisol mainly to the 20 beta-hydroxy acid. The results support our conclusion that both 17 alpha-hydroxy and 17-deoxy corticosteroids are oxidized to hydroxy acids by similar pathways and that isosteroids are obligatory intermediates.