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Endocrinology, Vol 137, 2167-2170, Copyright © 1996 by Endocrine Society

ARTICLES

Cloning and characterization of human urocortin [published erratum appears in Endocrinoogy 1996 Sep;137(9):3896]

CJ Donaldson, SW Sutton, MH Perrin, AZ Corrigan, KA Lewis, JE Rivier, JM Vaughan and WW Vale
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla 92037, USA.

Urocortin, a new member of the CRF peptide family which also includes urotensin I and sauvagine, was recently cloned from the rat midbrain. The synthetic replicate of urocortin was found to bind with high affinity to type 1 and type 2 CRF receptors and, based upon its anatomic localization within the brain, was proposed to be a natural ligand for the type 2 CRF receptors. Using a genomic library, we have cloned the human counterpart of rat urocortin and localized it to human chromosome 2. Human and rat urocortin share 95% identity within the mature peptide region. Synthetic human urocortin binds with high affinity to CRF receptor types 1, 2 alpha, and 2 beta, stimulates cAMP accumulation from cells stably transfected with these receptors, and acts in vitro to release ACTH from dispersed rat anterior pituitary cells. In addition, the CRF-binding protein binds human urocortin with high affinity and can prevent urocortin-stimulated ACTH secretion in vitro. The inhibitory effect of the CRF-binding protein on human urocortin can be blocked by biologically inactive CRF fragments, such as CRF(9-33).


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