A COMPARISON OF THE CLEARANCE OF OVINE AND HUMAN CORTICOTROPIN-RELEASING HORMONE (CRH) IN MAN AND SHEEP - A POSSIBLE ROLE FOR CRH-BINDING PROTEIN

A specific binding protein for human corticotrophin-releasing hormone (hCRH), which does not bind to the ovine hormone (oCRH), has recently been demonstrated in human plasma. No such binding protein has been found in sheep plasma. We have investigated the half-life of human and ovine CRH in man and in sheep. Peptides were measured directly in plasma with two-site immunoradiometric assays, as these assays are unaffected by the presence of inactivated peptide fragments. In man, the half-life of hCRH (30.5+/-3.3 min; mean +/- S.E.M.) Was significantly (P<0.001) less than that of oCRH (42.8+/-6.4 min). In sheep, there was no significant difference between the half-life of hCRH (46.5+/-7.2 min) and that of oCRH (39.8+/-10.1 min); these half-lives were also significantly (P<0.001) longer than that of hCRH in man. One possible explanation for the shorter half-life of hCRH in man is that the clearance of hCRH is enhanced by CRH-binding protein, although other binding proteins often have the opposite effect. Peak ACTH and cortisol responses occurred earlier in sheep than in man, although no differences were found in the response times to oCRH or hCRH within either species. The responses were more sustained in sheep than in man, and the previously reported biphasic response was only seen in some of the sheep and not in man. Absolute responses to either peptide were greater in sheep than in man; however, in man an 8.1-fold rise in ACTH was measured in response to oCRH, while hCRH gave a significantly (P=0.043) smaller 4.4-fold response. These experiments are discussed with particular reference to the effect of hCRH-binding protein and its possible role in potentiating the clearance of the peptide.