Role of the hypothalamic–pituitary–adrenal axis in developmental programming of health and disease
Open accessAbstract
Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth.
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Stress-induced neuroendocrine dysregulation of the maternal HPA-axis reflected by increased maternal cortisol levels is a potential mechanism underlying associations between depressive disorders and adverse outcomes, affecting the functioning of the neonatal HPA-axis.
“A potential mechanism underlying these associations is stress-induced neuroendocrine dysregulation of the maternal Hypothalamic Pituitary Adrenal (HPA)-axis reflected by increased maternal cortisol levels that, in turn, affects the functioning of the neonatal HPA-axis [11].”
From Effectiveness of a guided ACT-based self-help resilience training for depressive symptoms during pregnancy: Study protocol of a randomized controlled trial embedded in a prospective cohort. (2020) · cites this paper as [11]
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- Authors
- Xiong, F., & Zhang, L.
- Affiliations
- Loma Linda University Medical Center (US)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 34
- Issue
- 1
- Pages
- 27-46
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC3594480
- OpenAlex
- W2079889983
- Cited by
- 177
- References
- 330
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 17 · 2022: 16 · 2021: 10 · 2020: 19 · 2019: 12 · 2018: 17 · 2017: 11 · 2016: 9 · 2015: 12 · 2014: 16 · 2013: 7
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL057787, HL-082779, HL083966, R01HL082779, HL-089012, HL067745, HL-110125, R01HL089012, R01HL067745, R01HL083966, R01HL110125, R01HL118861)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-031226, P01HD031226)
- 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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hypothalamic-pituitary-adrenal axis, developmental programming, fetal programming, neonatal stress, glucocorticoid receptor, epigenetic regulation, hypoxic-ischemic encephalopathy, brain development, stress response, metabolism
- MeSH terms
- Animals, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Physiological, Epigenesis, Genetic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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