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Front Neuroendocrinol. 2011 Aug;32(3):265-86. doi: 10.1016/j.yfrne.2010.12.001. Epub 2010 Dec 7.

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

Author information

1
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK. cwyrwoll@staffmail.ed.ac.uk

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.

PMID:
21144857
PMCID:
PMC3149101
DOI:
10.1016/j.yfrne.2010.12.001
[Indexed for MEDLINE]
Free PMC Article
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