CORTICOTROPIN-RELEASING FACTOR-BINDING PROTEIN DIMERIZES AFTER ASSOCIATION WITH LIGAND

We have suggested recently that the fall in plasma CRF-binding protein (BP) during the last few weeks of pregnancy is a direct effect of ass ociation with its ligand because of the rapid decrease in plasma BP co ncentration seen in normal males reaching a nadir some 15 min after a bolus injection of synthetic CRF. In the present study, we have invest igated the physicochemical properties of both natural and recombinant BP by gel filtration under physiological conditions and have shown tha t association of human CRF to this BP results in an increase in molecu lar weight consistent with the formation of a dimer form of the BP lig and complex. The dimer is more stable when the interaction occurs in t he presence of serum or if a peptide with a higher affinity for the BP is substituted as ligand. Experimental evidence would also suggest th at the dimer BP has a higher affinity for ligand than the monomeric fo rm. We suggest that this dimerization occurs in vivo when CRF is relea sed into the bloodstream and provides the trigger that causes the upta ke of the complex at specific receptor sites.