11ß-hydroxysteroid dehydrogenases and the brain: from zero to hero, a decade of progress. (2011)

Abstract

Glucocorticoids have profound effects on brain development and adult CNS function. Excess or insufficient glucocorticoids cause myriad abnormalities from development to ageing. The actions of glucocorticoids within cells are determined not only by blood steroid levels and target cell receptor density, but also by intracellular metabolism by 11ß-hydroxysteroid dehydrogenases (11ß-HSD). 11ß-HSD1 regenerates active glucocorticoids from their inactive 11-keto derivatives and is widely expressed throughout the adult CNS. Elevated hippocampal and neocortical 11ß-HSD1 is observed with ageing and causes cognitive decline; its deficiency prevents the emergence of cognitive defects with age. Conversely, 11ß-HSD2 is a dehydrogenase, inactivating glucocorticoids. The major central effects of 11ß-HSD2 occur in development, as expression of 11ß-HSD2 is high in fetal brain and placenta. Deficient feto-placental 11ß-HSD2 results in a life-long phenotype of anxiety and cardiometabolic disorders, consistent with early life glucocorticoid programming.

Bibliographic Information

Digital Object Identifier: http://dx.doi.org/10.1016/j.yfrne.2010.12.001

PubMed Identifier: 21144857

Publication URI: http://europepmc.org/abstract/MED/21144857

Type: Journal Article/Review

Volume: 32

Parent Publication: Frontiers in neuroendocrinology

Issue: 3

ISSN: 0091-3022