The 11β-hydroxysteroid dehydrogenase system, a determinant of glucocorticoid and mineralocorticoid action
Oppermann UCT., Persson B., Jörnvall H.
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.