The Salk Institute for Biological Studies

University of Reading

Philip J Lowry

Wylie W Vale, Jr

Dominic P Behan

Wolfgang H Fischer

Ellen Potter

Elizabeth A Linton

Brain-derived membrane-associated CRF binding proteins

A Corticotropin Releasing Factor-binding protein (CRF-BP) is isolated and purified sufficient to provide AA sequence data from which the DNA is obtained, which is then used to produce the protein recombinantly. The CRF-BP is useful for modulating the biological activity of CRF, such as reducing the high ACTH levels in mammals caused by excess CRF. The CRF-BP or fragments thereof and/or antibodies to the proteins may be employed in diagnostic assays to determine the levels of CRF, CRF-BP and the ratio of CRF/CRF-BP in a vascular fluid sample. The DNA or subsequence thereof can be used as probes for genetic material in certain assays. The anti-CRF-BP antibodies are also useful to purify the CRF-BP protein and to modulate the biological effect of CRF-BPs proteins.

CRF binding protein

Corticotropin Releasing Factor-binding protein (CRF-BP) is produced recombinantly and is useful for modulating the biological activity of CRF. CRF-BP or fragments thereof and/or antibodies to such polypeptides are employed in diagnostic assays to determine the levels of CRF and CRF-BP and the ratio of CRF/CRF-BP in a vascular fluid sample. Following such an assay, pregnancy-related pathological disorders, such as increased risk of premature labor, can be treated, for example, by administering CRF-BP to lower the ratio of CRF/CRF-BP to within a normal range for pregnancy. Anti-CRF-BP antibodies are also useful to purify CRF-BP and to modulate the biological effect of CRF-BPs.

CRF binding protein antibodies and assays using same

Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.

DNA encoding CRF binding protein

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Reading, United Kingdom

Philip J Lowry