abstract |
A binding protein for Corticotropin Releasing Factor (CRF) is isolated from human plasma and partially sequenced. Using degenerate oligonucleotides based upon certain partial sequences of the isolated protein, the complete sequence for the 322-residue human precursor protein, termed CRF-BP, is deduced, which is believed to circulate in the plasma as an N-terminally shortened 298-residue mature protein. The homologous 322-residue sequence of the rat precursor protein is separately deduced. These proteins are produced recombinantly, and they are useful in the reduction of high ACTH levels in mammals caused by excess CRF and can be used to treat Cushing's Disease. They are also particularly useful in combating pituitary tumors which produce CRF and in modulating the various actions of CRF on the pituitary, the brain, the immune system and gastrointestinal blood flow. The proteins can also be used to raise blood pressure and combat hypotension in this manner. Antibodies to the proteins may be employed in diagnostic assays and in purification of the protein; they are also useful to counteract the biological effect of CRF-BPs. |