Glucocorticoid programming of pituitary-adrenal function: mechanisms and physiological consequences.

Increasing epidemiological evidence supports the notion that adverse events in fetal life permanently alter the structure and physiology of the adult offspring, a phenomenon dubbed 'fetal programming'. In particular, low weight or thinness at birth in humans is associated with an increased risk of cardiovascular and metabolic disorders as well as neuroendocrine dysfunction in adult life. Glucocorticoid administration during pregnancy is well-documented to both reduce offspring birth weight and alter the maturation of organs (hence their use to accelerate fetal lung maturation in premature labour). Here data are reviewed which show, in rodents and other models, that antenatal exposure to endogenous or exogenous glucocorticoids reduces offspring birth weight and produces permanent hypertension, hyperglycaemia, hyperinsulinaemia, altered behaviour and neuroendocrine responses throughout the lifespan. Processes underlying fetal programming include determination of the 'set point' of the hypothalamic-pituitary-adrenal (HPA) axis and of tissue glucocorticoid receptor (GR) expression. Similar HPA axis hyperreactivity occurs in lower birth weight humans and may be an early manifestation of the 'low birth weight' phenotype.