Fetal programming of the hypothalamic-pituitary-adrenal axis : is cortisol production upregulated centrally in low birthweight individuals?

Abstract

The first study compared three tests of central HPAA function in a group of low birthweight men aged 60-69 years from Hertfordshire, UK.  There were no differences in the free cortisol response to awakening or ACTH and cortisol responses during a 100μg corticotrophin-releasing hormone (CRH) test, but low birthweight men had significantly smaller pituitary-adrenal responses during a dexamethasone-suppressed CRH test.  While these findings do not explain the HPAA abnormalities associated with low birthweight in previous studies, they provide further evidence of dysregulation of the HPAA in men who were small at birth.

In further analysis of the data, blood pressure, glucose tolerance and plasma lipid concentrations were not related to these measures of central HPAA activity, despite significant positive correlations with morning cortisol concentrations.  These data suggest that other mechanisms, for example altered glucocorticoid metabolism, are responsible for elevating circulating cortisol concentrations in men with cardiovascular risk factors.

The second study explored cortisol and blood pressure responses to a series of psychological stress tests in a group of young men and women from Adelaide, Australia.  Cortisol responses were not related to size at birth in either sex, but in women there was a significant inverse relationship between birthweight and blood pressure reactivity.  This study provides the first human evidence that haemodynamic responses to psychological stress may be programmed antenatally, suggesting a potential mechanism linking reduced fetal growth with raised blood pressure and cardiovascular disease in later life.

In summary, this research does not support the idea that the HPAA is upregulated centrally in low birthweight individuals, but adds to the evidence that the activity of the axis may be influenced by factors affecting fetal growth.  The work presented in this thesis has added complexity to the role of the HPAA in the fetal origins of adult disease, and confirms that this is likely to remain an exciting area of research in years to come.

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