Prenatal Programming of Human Neurological Function

Figure 1

The regulation of the HPA axis changes dramatically over the course of gestation with profound implications for the mother and the fetus. One of the most significant changes during pregnancy is the development of the placenta, a fetal organ with significant endocrine properties. During pregnancy, CRH is released from the placenta into both the maternal and fetal compartments. In contrast to the negative feedback regulation of hypothalamic CRH, cortisol increases the production of CRH from the placenta. Placental CRH (pCRH) concentrations rise exponentially over the course of gestation. In addition to its effects on pCRH, maternal cortisol passes through the placenta. However, the effects of maternal cortisol on the fetus are modulated by the presence of p11βHSD2 which oxidizes it into an inactive form, cortisone. Activity of this enzyme increases as pregnancy advances and then drops precipitously so that maternal cortisol is available to promote maturation of the fetal lungs, central nervous system, as well as other organ systems.