THE METABOLISM OF ADRENOCORTICAL STEROIDS BY HUMAN TISSUES1

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Abstract
Adrenocortical steroids were incubated with preparations of human liver and term placenta and the metabolic products were isolated and characterized. Human liver homogenates interconverted cortisol and cortisone and reduced the latter substance to 5β-dihydrocortisone, tetrahydrocortisone and 20-dihydrocortisone. Tetrahydrocortisone was oxidized to 5β-dihydrocortisonc and reduced to cortolone. δ4-Reductase (5β) activity of human liver was found only in the soluble fraction while 3α-ol dehydrogenase activity against tetrahydrocortisone and llβ-ol dehydrogenase activity against cortisol were found concentrated in microsomal fractions. Placenta slices oxidized cortisol to cortisone, tetrahydrocortisone to 5β-dihydrocortisone, reduced tetrahydrocortisone to cortolone and, as in the case of liver, 3α-ol and llβ-ol dehydrogenases were associated with the microsomes. Further study of the microsomal dehydrogenase activities showed them to be reversible and to utilize pyridinc nucleotides as cofactors. Di- and triphosphopyridine nucleotides were equally effective in stimulating these activities of placental microsomes while with liver microsomes their relative effectiveness varied with the substrate studied. In addition to cortisol and tetrahydrocortisone, a variety of other 3α, 3β-, and 11β-hydroxysteroids were oxidized to the corresponding ketones by microsomes from both liver and placenta. These findings on the metabolic properties and biochemical characteristics of human tissues have been compared with the results obtained in studies of other species.