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Updated: Jun 25, 2026
13:22
A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
Epigenetic effects of glucocorticoids.
1Developmental Biology Program, Hospital for Sick Children, Toronto Medical Discovery East Tower, Medical & Related Sciences (MaRS) Centre, Toronto, Ontario, M5G 1X8, Canada. ian.weaver@utoronto.ca
Seminars in Fetal & Neonatal Medicine
|February 17, 2009
Summary
Early life experiences, like maternal care, shape lifelong stress responses and gene expression through epigenetic changes. These effects on the hypothalamic-pituitary-adrenal (HPA) axis are potentially reversible in adulthood.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- Early life environments significantly influence lifelong metabolic and endocrine functions.
- These effects are partly mediated by the programming of the hypothalamic-pituitary-adrenal (HPA) axis during infancy.
- Animal models demonstrate the lasting impact of maternal care on offspring's stress reactivity.
Purpose of the Study:
- To investigate the mechanisms by which early nurturing environments program HPA axis function.
- To explore the role of epigenetic modifications in mediating the long-term effects of maternal care.
- To determine if these environmentally induced epigenetic changes are reversible.
Main Methods:
- Utilized rat models to study variations in maternal care and their impact on HPA axis stress reactivity.
- Examined gene expression changes in offspring, focusing on glucocorticoid receptor expression.
- Investigated molecular mechanisms including histone acetylation, DNA demethylation, and the role of specific transcription factors.
- Employed cross-fostering and pharmacological interventions (TSA, l-methionine) to assess reversibility.
Main Results:
- Natural variations in maternal care led to long-term changes in offspring's HPA axis stress reactivity.
- Maternal licking and grooming increased offspring's hippocampal glucocorticoid receptor expression.
- These changes were linked to epigenetic modifications, including histone acetylation and DNA demethylation, mediated by nerve growth factor-inducible protein-A.
- Effects were reversed by cross-fostering and adult pharmacological treatments.
Conclusions:
- Early life experiences establish epigenetic states that influence lifelong phenotypes.
- Epigenetic modifications in response to environmental demands provide stable yet dynamic regulation.
- These findings highlight the potential reversibility of early-life programming through epigenetic mechanisms in adulthood.
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