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

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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

DOI 10.1016/j.yfrne.2010.12.001PMC PMC3149101

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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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Authors: Wyrwoll, C. S., Holmes, M. C., & Seckl, J. R.
Affiliations: The Queen's Medical Research Institute (GB)
Corresponding author: Wyrwoll, Caitlin S.
ORCID: Wyrwoll, Caitlin S.
Holmes, Megan C.
Seckl, Jonathan R.
Venue: Frontiers in Neuroendocrinology
Publisher: Elsevier BV
Published: 2011-08
Volume: 32
Issue: 3
Pages: 265-286
ISSN: 0091-3022 (ISSN-L)
DOI: 10.1016/j.yfrne.2010.12.001
PMC: PMC3149101
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: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/3.0/ (vor, 715 d)
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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11β-Hydroxysteroid dehydrogenases and the brain: From zero to hero, a decade of progress

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