Evidence of 11β-hydroxysteroid Dehydrogenase Type 2 Protein Expression and Enzymatic Activity in the Adult Rat Brain.

Intracellular glucocorticoid metabolism plays a critical role in shaping glucocorticoid receptor signaling in the brain. 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) catalyzes the NAD+-dependent oxidation of active glucocorticoids to inactive 11-keto forms, yet its expression and functional capacity in the adult brain are generally considered negligible, except for discrete brainstem nuclei. Here, we examined HSD11B2 expression in the adult rat brain at the mRNA and protein levels using quantitative real-time PCR, Western blotting, and immunohistochemistry. To assess catalytic function, HSD11B2 was immunoprecipitated from hippocampal lysates and assayed in vitro in the presence of NAD+, using cortisol as a substrate. Hsd11b2 mRNA and HSD11B2 protein were detected across all brain regions examined. Immunohistochemistry indicated predominant HSD11B2 immunoreactivity in hippocampal neurons. Both hippocampal homogenates and HSD11B2 immunoprecipitates displayed NAD+-dependent glucocorticoid dehydrogenase activity, consistent with enzymatic functionality. Collectively, these findings provide molecular and functional evidence for HSD11B2 expression and activity in the adult rat brain and motivate further studies to define its cellular localization and to clarify how local glucocorticoid inactivation influences hippocampal signaling and physiology.