74 Central cortisol regulation in pregnancy

Abstract

Pregnancy is characterized by changes in the regulation of the maternal hypothalamic-pituitary-adrenal (HPA) axis. Even though it is known that aberrations in this pathway could have implications for mood disorders during pregnancy, the effects of cortisol on the maternal brain in healthy women are poorly understood. Therefore, we aimed to enhance our understanding of central adaptations in cortisol metabolism in healthy pregnant women at term gestation. Plasma and CSF cortisol and cortisone were prospectively collected in 24 women at term gestation prior to scheduled cesarean section and in 24 regularly cycling non-pregnant controls matched for age and BMI. Subjects were healthy, with no history of smoking, alcoholism, psychiatric or neurological disorders. Cortisol and cortisone (inactivated form) were assayed by ELISA. Data were analyzed by two-tailed Student t test. Plasma cortisol levels were 54% higher (248.5±15.9 vs 161.7±10.7 ng/ml, p<0.001) and plasma cortisone levels were 88% higher (110.9±7.7 vs 59.1± 6.1 ng/ml, p <0.001) in pregnant vs non-pregnant women, as expected. In CSF, cortisol (7.7 ± 0.5 vs 6.1 ± 0.3 ng/mL, p = 0.01) and cortisone (8.2 ± 0.9 vs 2.7 ± 0.2 ng/mL, p < 0.001) were also significantly higher in pregnant vs non-pregnant subjects. However, interestingly, in pregnant subjects the relative increase in CSF cortisol was only ½ that observed in plasma, while the relative increase in CSF cortisone was 2.3 times greater than in plasma. Accordingly, the CSF cortisol/cortisone ratio was significantly lower in pregnancy (1.30 ± 0.3 vs 2.4 ± 0.2, p = 0.003), due to the increased concentration of the inactive metabolite cortisone. To our knowledge, this is the first study to measure CSF cortisol and cortisone concentrations in pregnancy. These data demonstrate a pregnancy-specific shift in central cortisol metabolism that favors cortisone. This adaptation may protect the maternal brain from high cortisol levels, and aberrations in this pathway could have implications for mood disorders during pregnancy and post-partum.