11Beta-hydroxysteroid Dehydrogenases: a Novel Control of Glucocorticoid Action in the Brain

Clearly the actions of 11beta-HSDs in the CNS are only beginning to be unraveled, though some principles are emerging. 11Beta-hydroxysteroid dehydrogenase type 2 inactivates glucocorticoids but is found only in a few very restricted sites in the adult brain. Its role in the fetal CNS is likely to be more extensive, but is largely unexplored. 11Beta-hydroxysteroid dehydrogenase type 1 is a reductase in CNS cells and amplifies glucocorticoid action. The striking protection against cognitive decline seen in elderly 11beta-HSD1 knockout mice suggest that manipulation of this isozyme may be a useful therapeutic avenue to explore.