UROCORTIN, A MAMMALIAN NEUROPEPTIDE RELATED TO FISH UROTENSIN-I AND TO CORTICOTROPIN-RELEASING FACTOR

Corticotropin-releasing factor (CRF), a peptide first isolated from ma mmalian brain(1), is critical in the regulation of the pituitary-adren al axis, and in complementary stress-related endocrine, autonomic and behavioural responses(2). Fish urotensin I and amphibian sauvagine wer e considered to be homologues(3) of CRF until peptides even more close ly related to CRF were identified in these same vertebrate classes(4,5 ). We have characterized another mammalian member of the CRF family an d have localized its urotensin-like immunoreactivity to, and cloned re lated complementary DNAs from, a discrete rat midbrain region. The ded uced protein encodes a peptide that we name urocortin, which is relate d to urotensin (63% sequence identity) and CRF (45% sequence identity) . Synthetic urocortin evokes secretion of adrenocorticotropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected t ype-1 CRF receptors(6,9), the subtype expressed by pituitary corticotr opes. The coincidence of urotensin-like immunoreactivity with type-2 C RF receptors(10-13) in brain, and our observation that urocortin is mo re potent than CRF at binding and activating type-2 CRF receptors, as well as at inducing c-Fos (an index of cellular activation) in regions enriched in type-2 CRF receptors, indicate that this new peptide coul d be an endogenous ligand for type-2 CRF receptors.