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Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis: low birth weight and central HPA regulation

Alexandra M V Ward1, Holly E Syddall, Peter J Wood

  • 1Medical Research Council Environmental Epidemiology Unit, Southampton General Hospital, Southampton, SO16 6YD, United Kingdom.

The Journal of Clinical Endocrinology and Metabolism
|March 6, 2004
PubMed

Insights

Men with low birth weight (LBW) show altered hypothalamic-pituitary-adrenal (HPA) axis regulation in later life. Specifically, LBW men exhibited reduced pituitary-adrenal responses in a dexamethasone-suppressed corticotropin-releasing hormone (DEX/CRH) test.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Human Physiology

Background:

  • Fetal programming links reduced fetal growth to adult cardiovascular and metabolic diseases.
  • Low birth weight (LBW) is associated with increased fasting cortisol and adrenal responsiveness.
  • The hypothalamic-pituitary-adrenal (HPA) axis is a key pathway in this association.

Purpose of the Study:

  • To investigate HPA axis regulation in older men based on birth weight.
  • To compare salivary cortisol, ACTH, and cortisol responses to CRH stimulation and DEX/CRH tests between LBW and high birth weight (HBW) men.

Main Methods:

  • Evaluated salivary cortisol response to awakening.
  • Assessed plasma ACTH and cortisol responses to CRH stimulation.
  • Administered a dexamethasone-suppressed CRH (DEX/CRH) test.

Main Results:

  • No significant differences in basal pituitary-adrenal activity or ACTH/cortisol responses to CRH between LBW and HBW men.
  • LBW men demonstrated significantly lower pituitary-adrenal responses during the DEX/CRH test.
  • Findings suggest HPA axis dysregulation in individuals with a history of LBW.

Conclusions:

  • The DEX/CRH test revealed altered HPA axis regulation in LBW men, indicating potential long-term programming effects.
  • While not fully explaining previous HPA abnormalities in LBW, these results provide further evidence of HPA axis dysregulation.
  • This study contributes to understanding the long-term health consequences of fetal growth restriction.

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