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

Front Neuroendocrinol. 2013 Jan;34(1):27-46. doi: 10.1016/j.yfrne.2012.11.002. Epub 2012 Nov 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology*
  • Humans
  • Hypothalamo-Hypophyseal System / embryology
  • Hypothalamo-Hypophyseal System / growth & development
  • Hypothalamo-Hypophyseal System / metabolism*
  • Pituitary-Adrenal System / embryology
  • Pituitary-Adrenal System / growth & development
  • Pituitary-Adrenal System / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Stress, Physiological / physiology*


  • Receptors, Glucocorticoid