Nick Hales Award Lecture 2011: glucocorticoids and early life programming of cardiometabolic disease

R. M. Reynolds*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Epidemiological studies have demonstrated an association between low birthweight and a range of diseases in adult life including cardiometabolic and psychiatric diseases. One of the key mechanisms proposed to underlie early life 'programming' of disease is overexposure of the developing foetus to glucocorticoids. This review will explore the data from human studies that glucocorticoids are not only mediators of programming, but also targets of programming. Cohort studies of men and women of known birthweight have demonstrated that low birthweight is associated with high fasting cortisol levels. In healthy individuals and in people with type 2 diabetes who are at high cardiovascular risk, there is a similar association between high fasting cortisol and the metabolic syndrome. The high cortisol levels appear to be due to activation of the hypothalamic-pituitary-adrenal (HPA) axis though detailed studies to further explore central negative feedback sensitivity are required. The evidence in humans that glucocorticoids mediate programming is more scanty, though changes in maternal body composition, stress and anxiety levels and activity of the placental barrier enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) may all influence maternal HPA axis activity. Emerging studies are supportive that high maternal cortisol levels in humans and/or deficiencies placental 11 beta-HSD2 humans are associated with lower birthweight and adverse metabolic and neurocognitive outcomes in the offspring.

Original languageEnglish
Pages (from-to)309-314
Number of pages6
JournalJournal of Developmental Origins of Health and Disease
Volume3
Issue number5
DOIs
Publication statusPublished - Oct 2012

Keywords

  • ADULT LIFE
  • RISK-FACTORS
  • LOW-BIRTH-WEIGHT
  • STRESS
  • BLOOD-PRESSURE
  • cardiometabolic disease
  • PLASMA-CORTISOL CONCENTRATIONS
  • HEART-DISEASE
  • METABOLIC SYNDROME
  • glucocorticoids
  • programming
  • MESSENGER-RNA EXPRESSION
  • CORONARY-ARTERY-DISEASE

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