Development of the fetal hypothalamic-pituitary-adrenal-placental axis: Implications for postnatal health

Late pregnancy is a period of stress, not only for the mother, but also for the fetus. At this time, there is an acute maturation and activation of hypothalamic-pituitaryadrenal (HPA) axis activity in the fetus with a consequent increase in the concentration of cortisol in the fetal circulation, and increased output of adrenalin from the fetal adrenal medulla. In this article, we focus on the significance of changes in fetal adrenal glucocorticoid (GC) output, in human and in sheep pregnancy, and on the relationship between endocrine activities in the fetus with the endocrine functions of the placenta. Fetal Hypothalamic-Pituitary-Adrenal Maturation Bassett and Thorburn [1] first reported the dramatic exponential rise in plasma cortisol that occurs in the circulation of the sheep fetus during the latter part of normal gestation. Later, we [2, 3] and others [4] showed that this was associated with a progressive increase in the concentration of adrenocorticotrophin 1–39 (ACTH) in the circulation of the fetus in a manner that was consistent with the latter driving the increase in fetal adrenal function. Fowden et al. [5] have provided a detailed review of the consistency of this change in plasma GC across animal species. In the human, as in the sheep, the major steroid secreted is cortisol, whereas in the rat and mouse