Cited by 244Stress Responses and CortisolHormonal Regulation and HypertensionAdrenal Hormones and Disorders

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

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Wyrwoll, Caitlin S., Holmes, Megan C., Seckl, Jonathan R.·2011·Frontiers in Neuroendocrinology

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.

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Crossref · 10.1016/j.yfrne.2010.12.001

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  • 11β-HSD type 1 generates bioactive glucocorticoids from inactive 11-keto derivatives while type 2 catalyzes the opposite reaction; type 1 is widely expressed by neurons and glial cells, whereas type 2 expression is more restricted.

    “Briefly, 11β-HSD type 1 generates the bioactive form (cortisol or corticosterone) from inactive 11-keto derivatives while 11β-HSD type 2 catalyzes the opposite reaction. Interestingly, 11-keto derivatives do not bind to CBG in plasma nor are expelled by the efflux pumps of the BBB. As a result, 11-keto-GCs reach the CNS more readily than the bioactive form. 11β-HSD type 1 is widely expressed by”

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Research works printed but not linked: 1

  1. [142]Langley-Evans S.C. Philips G. Benediktsson R. Gardner D. Edwards C.R.W. Jackson A.A. Seckl J.R. Maternal dietary protein restriction, placental glucocorticoid metabolism and the programming of hypertension Placenta 17 1996 169 172 8730887

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Authors
Wyrwoll, C. S., Holmes, M. C., & Seckl, J. R.
Affiliations
The Queen's Medical Research Institute (GB)
Corresponding author
Wyrwoll, Caitlin S.
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2011-08
Volume
32
Issue
3
Pages
265-286
ISSN
0091-3022 (ISSN-L)
OpenAlex
W2133069858
Cited by
244
References
336
Citations by year
2026: 9 · 2025: 12 · 2024: 10 · 2023: 17 · 2022: 12 · 2021: 18 · 2020: 18 · 2019: 22 · 2018: 12 · 2017: 15 · 2016: 20 · 2015: 17 · 2014: 22 · 2013: 23 · 2012: 12
FWCI
1.10
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Neuroendocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Wellcome Trust
  • MRC
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
11β-hydroxysteroid dehydrogenase, 11β-hydroxysteroid dehydrogenase type 1, 11β-hydroxysteroid dehydrogenase type 2, glucocorticoids, brain development, cognitive aging, hippocampus, neocortex, placenta, fetal programming, anxiety, cardiometabolic disease, glucocorticoid metabolism
MeSH terms
Aging, Animals, Brain, Glucocorticoids, Humans, Isoenzymes, Signal Transduction, Gene Expression Regulation, Enzymologic, 11-beta-Hydroxysteroid Dehydrogenase Type 1, 11-beta-Hydroxysteroid Dehydrogenase Type 2

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