11β-hydroxysteroid dehydrogenases and the brain: from zero to hero, a decade of progress

Caitlin S. Wyrwoll, Megan C. Holmes, Jonathan R. Seckl

Research output: Contribution to journalLiterature reviewpeer-review

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 11β-hydroxysteroid dehydrogenases (11β-HSD). 11β-HSD1 regenerates active glucocorticoids from their inactive 11-keto derivatives and is widely expressed throughout the adult CNS. Elevated hippocampal and neocortical 11β-HSD1 is observed with ageing and causes cognitive decline; its deficiency prevents the emergence of cognitive defects with age. Conversely, 11β-HSD2 is a dehydrogenase, inactivating glucocorticoids. The major central effects of 11β-HSD2 occur in development, as expression of 11β-HSD2 is high in fetal brain and placenta. Deficient feto-placental 11β-HSD2 results in a life-long phenotype of anxiety and cardiometabolic disorders, consistent with early life glucocorticoid programming.
Original languageEnglish
Pages (from-to)265-286
Number of pages22
JournalFrontiers in neuroendocrinology
Volume32
Issue number3
DOIs
Publication statusPublished - Aug 2011

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