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Role of the hypothalamic-pituitary-adrenal axis in developmental programming of health and disease

Fuxia Xiong1, Lubo Zhang

  • 1Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, United States.

Frontiers in Neuroendocrinology
|December 4, 2012
PubMed

Insights

Early life stress can permanently alter the hypothalamic-pituitary-adrenal (HPA) axis through epigenetic changes to the glucocorticoid receptor (GR) gene, increasing disease risk later in life.

Area of Science:

  • Developmental biology
  • Neuroendocrinology
  • Epigenetics

Background:

  • Adverse early life environments can permanently program physiology and metabolism.
  • Programming of the hypothalamic-pituitary-adrenal (HPA) axis is a key mechanism linking early stress to later disease.
  • Epigenetic modifications of the glucocorticoid receptor (GR) gene promoter are central to HPA axis programming.

Purpose of the Study:

  • To review current research on HPA axis programming and adult health/disease.
  • To focus on epigenetic regulation of GR gene expression following fetal/neonatal stress.
  • To examine the impact of aberrant GR gene expression on brain development and protection.

Main Methods:

  • Literature review of studies on HPA axis programming.
  • Analysis of epigenetic mechanisms regulating glucocorticoid receptor (GR) gene expression.
  • Examination of the role of GR in protecting the developing brain.

Main Results:

  • Fetal and neonatal stress can lead to permanent programming of the HPA axis.
  • Epigenetic modifications of the GR gene promoter influence GR expression and stress response.
  • Aberrant GR gene expression in the developing brain impairs protection against hypoxic-ischemic encephalopathy.

Conclusions:

  • Early life stress-induced HPA axis programming, via GR epigenetic changes, contributes to adult disease risk.
  • Understanding these epigenetic mechanisms is crucial for preventing long-term health consequences.
  • Targeting GR gene expression may offer protective strategies for the developing brain during critical neonatal periods.

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