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Heterogeneity of the Human Corticotropin-Releasing Factor-Binding Protein

School of Animal and Microbial Sciences, University of Reading (R.J.W., C.F.K., P.J.L.), Whiteknights, Reading RG6 6AJ; and the Department of Rheumatology, Battle Hospital (J.D.), Reading RG30 IAG, United Kingdom

Address all correspondence and requests for reprints to: Dr. R. J. Woods, School of Animal and Microbial Sciences, University of Reading, Whiteknights, P.O. Box 228, Reading, United Kingdom RG6 6AJ.

Human corticotropin-releasing factor (hCRF), secreted by the placenta, principally in the third trimester, is specifically bound in the peripheral circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from the circulation. We postulate that the protein may be returned to the blood in a form that is immunologically altered and not well recognized by the reported RIAs. We report that a stable isoform can result from temporary denaturation of recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein, which can bind CRF, has been found to bind to an antibody raised against a synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not to a second similar N-terminal antibody, although it was closely matched in titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF-BP. It is proposed that as a result of in vivo post-ligand binding events, isoforms may be susceptible to cleavage. After affinity purification, which involves denaturation, recombinant CRF-BP was often found to be cleaved after storage in the presence of protease inhibitors.

Here we present evidence for a C-terminally truncated form of the native binding protein in the plasma of subjects suffering from rheumatoid arthritis, which may parallel the in vitro truncation.

This article has been cited by other articles:

				R. J. Woods, C. F. Kemp, J. David, I. G. Sumner, and P. J. Lowry Cleavage of Recombinant Human Corticotropin-Releasing Factor (CRF)-Binding Protein Produces a 27-Kilodalton Fragment Capable of Binding CRF J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2788 - 2794. [Abstract] [Full Text]