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| CLONING AND CHARACTERIZATION OF THE CDNAS FOR HUMAN AND RAT CORTICOTROPIN RELEASING FACTOR-BINDING PROTEINS |
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| Author(s): POTTER E, BEHAN DP, FISCHER WH, LINTON EA, LOWRY PJ, VALE WW |
| Source: NATURE Volume: 349 Issue: 6308 Pages: 423-426 Published: JAN 31 1991 |
| Times Cited: 238 References: 33 |
| 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 low 2-4, they increase throughout pregnancy 4-8 and fall rapidly after parturition. Maternal plasma CRF probably originates from the placenta, which responds to the bioactive peptide 5, 9, 10 and produces the peptide 9 and its messenger RNA 11. Even though CRF concentrations in late gestational maternal plasma are similar to those in rat hypothalamic portal blood 12,13 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 range 14. Several groups have now reported the existence of a CRF-binding protein in human plasma which inactivates CRF 15-20 and which has been proposed to prevent inappropriate pituitary-adrenal stimulation in pregnancy. The binding protein was recently purified from human plasma 19. 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 protein 15. 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: POTTER, E (reprint author), SALK INST BIOL STUDIES, CLAYTON FDN PEPTIDE BIOL, LA JOLLA, CA 92138 USA |
Addresses:
1. UNIV CALIF SAN DIEGO, DEPT PHARMACOL, LA JOLLA, CA 92037 USA
2. UNIV READING, SCH ANIM & MICROBIAL SCI, DEPT BIOCHEM & PHYSIOL, READING RG6 2AJ, BERKS ENGLAND |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: EV514 |
| ISSN: 0028-0836 |
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