The 11β‐Hydroxysteroid Dehydrogenase System, A Determinant of Glucocorticoid and Mineralocorticoid Action

Abstract

Enzymatic interconversion of active and inactive glucocorticoid hormone is important, and is carried out physiologically by 11β‐hydroxysteroid dehydrogenase (11β‐HSD) isoforms, explaining their role in cellular and toxicological processes. Two forms of the enzyme, 11β‐HSD‐1 and 11β‐HSD‐2, belonging to the protein superfamily of short‐chain dehydrogenases/reductases, have been structurally and functionally characterised. Although displaying dehydrogenase and reductase activities in vitro, the dominant in vivo function of the type‐1 enzyme might be to work as a reductase, thus generating active cortisol from inactive cortisone precursors. On the other hand, for adrenal glucocorticoids the type‐2 enzyme seems to be exclusively a dehydrogenase and, by inactivating glucocorticoids, confers specificity to peripheral mineralocorticoid receptors.