Detection of N-terminal pro-corticotrophin releasing hormone (CRH) and a 'Novel' CRH in human maternal plasma and placenta

Corticotrophin-releasing hormone (CRH) is released from the human placenta in high concentrations towards the end of the third trimester of pregnancy, but relative concentrations of other cleavage products derived from the CR H prohormone are unknown. We have measured CRH and N-terminal (1-100) and ( 1-127) proCRH peptides in maternal plasma in the second and third trimester s of pregnancy and in term placental extract using immunoradiometric assays (IRMAs) specific to different regions of the CRH precursor. Levels of N-te rminal proCRH (amino acid residues 1-100) rose from 24 +/- 4 pmol/l (mean /- s.c.) in the second trimester to 378.8 +/- 65 pmol/l (mean +/- s.e.) at term. Levels of intact proCRH and/or (1-127) proCRH remained relatively con stant throughout the second and third trimesters, with a concentration of 2 9.3 +/- 3.8 pmol/l (mean +/- s.e.). In the course of this work a novel form of CRH that cross-reacts within specific CRH immunoassays was observed. Th e use of two IRMAs developed for CRH (1-41) having different C-terminal epi tope specificities provided evidence for two types of CRH coexisting in mat ernal plasma. Separation of term placental extract by HPLC and application of the two CRH IRMAs revealed two peaks of immunoreactivity one of which co eluted with synthetic CRH (1-41). (C) 2000 Harcourt Publishers Ltd.