11beta-Hydroxysteroid dehydrogenase type 2 protects the neonatal cerebellum from deleterious effects of glucocorticoids

Neuroscience. 2006 Feb;137(3):865-73. doi: 10.1016/j.neuroscience.2005.09.037. Epub 2005 Nov 14.


11beta-Hydroxysteroid dehydrogenase type 2 is a glucocorticoid metabolizing enzyme that catalyzes rapid inactivation of corticosterone and cortisol to inert 11-keto derivatives. As 11beta-hydroxysteroid dehydrogenase type 2 is highly expressed in the developing brain, but not in the adult CNS, we hypothesized that it may represent a protective barrier to the deleterious actions of corticosteroids on proliferating cells. To test this hypothesis we have investigated the development and growth of the cerebellum in neonatal C57BL/6 mice and mice lacking 11beta-hydroxysteroid dehydrogenase type 2 (-/-). 11beta-Hydroxysteroid dehydrogenase type 2-/- mice had consistently lower body weight throughout the neonatal period, coupled with a smaller brain size although this was normalized when corrected for body weight. The cerebellar size was smaller in 11beta-hydroxysteroid dehydrogenase type 2-/- mice, due to decreases in size of both the molecular and internal granule layers. When exogenous corticosterone was administered to the pups between postnatal days 4 and 13, 11beta-hydroxysteroid dehydrogenase type 2(-/-) mice were more sensitive, showing further inhibition of cerebellar growth while the wildtype mice were not affected. Upon withdrawal of exogenous steroid, there was a rebound growth spurt so that at day 21 postnatally, the cerebellar size in 11beta-hydroxysteroid dehydrogenase type 2-/- mice was similar to untreated mice of the same genotype. Furthermore, 11beta-hydroxysteroid dehydrogenase type 2-/- mice had a delay in the attainment of neurodevelopmental landmarks such as negative geotaxis and eye opening. We therefore suggest that 11beta-hydroxysteroid dehydrogenase type 2 acts as to protect the developing nervous system from the deleterious consequences of glucocorticoid overexposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / biosynthesis
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 / physiology*
  • Animals
  • Animals, Newborn / physiology*
  • Body Weight / physiology
  • Brain / enzymology
  • Brain / growth & development
  • Cell Proliferation
  • Cerebellum / growth & development
  • Cerebellum / pathology
  • Cerebellum / physiology*
  • Corticosterone / blood
  • Female
  • Glial Fibrillary Acidic Protein / biosynthesis
  • Glucocorticoids / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size / physiology
  • Postural Balance / physiology
  • Reflex / physiology


  • Glial Fibrillary Acidic Protein
  • Glucocorticoids
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Corticosterone