The actions of glucocorticoids can be terminated by conversion of these steroids to biologically inactive forms. The processes by which these steroids are inactivated involve a number of enzymes and tissues. The importance of alterations in the metabolic degradation of adrenal steroids in human physiology and disease states is becoming increasingly clear and will be reviewed here.
Adrenal steroid biosynthesis is reviewed separately. (See "Adrenal steroid biosynthesis".)
Hepatic — The major site of cortisol metabolism is the liver. There cortisol is reduced, oxidized, or hydroxylated, and the products of these reactions are made water soluble by conjugation with sulfate or glucuronic acid to facilitate their excretion in urine (figure 1). Gas chromatography with mass spectrometry (GC/MS) has provided quantitative data on the urinary excretion of each of these cortisol metabolites, allowing identification of a number of inherited and acquired disorders characterized by abnormal glucocorticoid dynamics .
Reduction — Cortisol is inactivated mainly by reductive disruption of its 3-keto, delta-4 double bond structure. Reduction reactions can also result in “regeneration” of cortisol from its inactive metabolite, cortisone.
●Reduction of the keto group, with formation of a 3-hydroxyl group, is carried out by 3 alpha hydroxysteroid dehydrogenase.
●Reduction of the cortisol A ring double bond, which results in an asymmetric carbon atom at position 5, is carried out by 5 alpha-reductase (of which there are two isoforms expressed in liver) and 5 beta-reductase.