Antenatal Glucocorticoids and Programming of the Developing CNS

Glucocorticoids (GCs) are essential for many aspects of normal brain development. However, there is growing evidence from a number of species that exposure of the fetal brain to excess GC, at critical stages of development, can have life-long effects on behavior and neuroendocrine function. The hypothalamo-pituitary-adrenal axis, which is central to the integration of the individual's endocrine and behavioral response to stress, appears highly sensitive to excess GC exposure during development. A number of animal studies have shown that exposure to synthetic GCs in utero results in adult offspring that exhibit hyperactivity of the hypothalamo-pituitary-adrenal axis. This will have a long-term impact on health, inasmuch as increased life-long exposure to endogenous GC has been linked to the premature onset of diseases associated with aging. The mechanisms involved in the permanent programming of hypothalamo-pituitary-adrenal function and behavior are not well understood. Synthetic GCs are used extensively to promote pulmonary maturation in fetuses at risk of being delivered before term. Therefore, it is important that we understand the potential long-term consequences of prenatal GC exposure on brain development as well as the underlying mechanisms involved. This review will explore the current state of knowledge in this rapidly expanding field.