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Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins

Abstract

CORTICOTROPIN-releasing factor (CRF)1, is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRF concentrations in the human peripheral circulation are normally low2–4, they increase throughout pregnancy4–8 and fall rapidly after parturition. Maternal plasma CRF probably originates from the placenta, which responds to the bioactive peptide5,9,10 and produces the peptide9and its messenger RNA11. Even though CRF concentrations in late gestational maternal plasma are similar to those in rat hypothalamic portal blood12,13 and to those that can stimulate release of adrenocorticotropic hormone (ACTH) in vitro, maternal plasma ACTH concentrations increase only slightly with advancing gestation and remain within the normal range14. Several groups have now reported the existence of a CRF-binding protein in human plasma which inactivates CRF15–20 and which has been proposed to prevent inappropriate pituitary-adrenal stimulation in pregnancy. The binding protein was recently purified from human plasma19. We have now isolated and partially sequenced the binding protein, allowing us to clone and characterize its complementary DNA from human liver and rat brain. Expression of the cDNAs for human and rat binding protein in COS7 cells showed that these proteins bind CRF with the same affinity as the native human protein15. Both rat and human recombinant binding proteins inhibit CRF binding to a CRF antibody and inhibit CRF-induced ACTH release by pituitary cells in vitro.

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Potter, E., Behan, D., Fischer, W. et al. Cloning and characterization of the cDNAs for human and rat corticotropin releasing factor-binding proteins. Nature 349, 423–426 (1991). https://doi.org/10.1038/349423a0

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