Corticotrophin-releasing hormone-binding protein in human fetal plasma

During pregnancy maternal plasma corticotrophin-releasing hormone (CRH) levels rise 1000-fold whilst fetal plasma levels are often 100-fold higher than the concentrations seen in normal non-pregnant human plasma. Despite these high CRH levels neither the maternal nor fetal pituitary releases excessive amounts of ACTH. A specific CRH-binding protein (CRHBP) exists in the maternal circulation which is able to bind and inactivate the ACTH releasing activity of CRH. In this study we have used a specific CRHBP radioimmunoassay to determine the level of CRHBP in fetal and maternal plasma samples. Fetal samples were collected by cordocentesis between 20 and 33 weeks gestation and matched maternal samples were taken by venepuncture at the same time. In a second study, plasma samples were collected from 8 women at fortnightly intervals from week 20 to term, at labour and post-partum. A fetal sample, taken from the umbilical vein, was collected immediately post-delivery. The mean maternal CRHBP concentration for the samples collected between 20 and 33 weeks (n = 23) was 8.12 nmol/l and the fetal level was 8.62 nmol/l. Data from the second study showed that at term the maternal CRHBP concentration decreased significantly (P < 0.025) to 6.32 nmol/l. The fetal CRHBP level also decreased significantly (P < 0.001) at term to a level of 5.84 nmol/l. The CRHBP in both fetal and maternal plasma was shown to be functional by 125I-CRH binding and gel permeation chromatography. The capacity of maternal and fetal plasma to bind 125I-CRH decreased at term in agreement with the quantitation of plasma CRHBP by radioimmunoassay.