title: Association of human corticotropin-releasing hormone to its binding protein in blood may trigger clearance of the complex.
abstract: Late in the last trimester of human pregnancy, as plasma CRH levels rise, the concentration of circulating CRH-binding protein (CRH-BP) falls. We have investigated, using nonpregnant subjects, the hypothesis that CRH has a negative effect on plasma levels of CRH-BP. A specific RIA developed with the aid of recombinant binding protein has been used to measure CRH-BP. Subjects given iv infusions of human CRH for 10 h showed a sustained fall in plasma CRH-BP for the duration of the infusion. Intravenous bolus injection of human CRH produced a rapid reduction in CRH-BP levels to 54% of the basal value, whereas ovine CRH was without effect, even though both peptides are cleared from the plasma at similar rates and have similar effects on the pituitary-adrenal axis. The rapid clearance was concluded to be related to ligand affinity, as ovine CRH has a 200-fold lower affinity than human CRH for CRH-BP. We suggest that the rising levels of CRH are responsible for the reduction in CRH-BP concentrations observed in late pregnancy, and that this reduction is triggered by the binding of CRH-BP to its ligand.
authors.affiliation: Department of Biochemistry and Physiology, University of Reading, Whiteknights, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Woods
authors.forename: A
authors.initials: A
authors.lastname: Grossman
authors.forename: P
authors.initials: P
authors.lastname: Saphier
authors.forename: K
authors.initials: K
authors.lastname: Kennedy
authors.forename: E
authors.initials: E
authors.lastname: Ur
authors.forename: D
authors.initials: D
authors.lastname: Behan
authors.forename: E
authors.initials: E
authors.lastname: Potter
authors.forename: W
authors.initials: W
authors.lastname: Vale
authors.forename: P J
authors.initials: PJ
authors.lastname: Lowry
mesh_terms: D000818:Animals; D016466:CHO Cells; D003346:Corticotropin-Releasing Hormone / Q000097:blood* / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008024:Ligands; D008297:Male; D011863:Radioimmunoassay; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D012756:Sheep
chemical_list: D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone