Glucocorticoid Programming
Abstract
Epidemiological evidence suggests that an adverse fetal environment permanently programs physiology, leading to increased risks of cardiovascular, metabolic, and neuroendocrine disorders in adulthood. Prenatal glucocorticoid excess or stress might link fetal maturation and adult pathophysiology. In a variety of animal models, prenatal glucocorticoid exposure or inhibition of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the fetoplacental "barrier" to maternal glucocorticoids, reduces birth weight and causes permanent hypertension, hyperglycemia, and increased hypothalamic-pituitary-adrenal axis (HPA) activity and behavior resembling anxiety. In humans, 11beta-HSD2 gene mutations cause low birth weight and reduced placental 11beta-HSD2 activity associated with intrauterine growth retardation. Low birth weight babies have higher plasma cortisol levels throughout adult life, indicating HPA programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors; key is the glucocorticoid receptor itself. Differential programming of the glucocorticoid receptor in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the glucocorticoid receptor gene. Overall, the data suggest that either pharmacological or physiological exposure to excess glucocorticoids prenatally programs pathologies in adult life.
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The brain changes dramatically during fetal development and is vulnerable to environmental insults.
“Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults.”
From High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children. (2010) · cites this paper as Seckl & Meaney, 2004
The relationship between quality of early social environment and adult health appears partly mediated by development of individual differences in neural systems underlying behavioral and endocrine stress responses.
“The relationship between the quality of the early social environment and health in adulthood appears to be, in part, mediated by the development of individual differences in neural systems that underlie the expression of behavioral and endocrine responses to stress.26-30”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [26]
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- Authors
- SECKL, J. R., & MEANEY, M. J.
- Affiliations
- Douglas Mental Health University Institute (CA)
- Corresponding author
- SECKL, JONATHAN R.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2004-12
- Volume
- 1032
- Issue
- 1
- Pages
- 63-84
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W4210953733
- Cited by
- 556
- References
- 7
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 14 · 2023: 16 · 2022: 26 · 2021: 19 · 2020: 18 · 2019: 24 · 2018: 17 · 2017: 21 · 2016: 33 · 2015: 18 · 2014: 30 · 2013: 40 · 2012: 44
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- fetal programming, prenatal glucocorticoid exposure, 11β-hydroxysteroid dehydrogenase type 2, low birth weight, fetal growth restriction, hypertension, hyperglycemia, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, transcription factors, fetal stress, anxiety-like behavior, cardiovascular risk, metabolic disease risk
- MeSH terms
- Behavior, Birth Weight, Cardiovascular Physiological Phenomena, Central Nervous System, Female, Glucocorticoids, Humans, Infant, Newborn, Infant, Premature, Metabolism, Pregnancy, Prenatal Exposure Delayed Effects, Stress, Physiological, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Fetal Development
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