Donaldson C J, Sutton S W, Perrin M H, Corrigan A Z, Lewis K A, Rivier J E, Vaughan J M, Vale W W
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla 92037, USA.
Endocrinology. 1996 May;137(5):2167-70. doi: 10.1210/endo.137.5.8612563.
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).
尿皮质素是促肾上腺皮质激素释放因子（CRF）肽家族的新成员，该家族还包括尾加压素I和蛙皮素，最近从大鼠中脑克隆得到。研究发现，尿皮质素的合成复制物能与1型和2型CRF受体高亲和力结合，基于其在脑内的解剖定位，推测它是2型CRF受体的天然配体。利用基因组文库，我们克隆了大鼠尿皮质素的人类对应物，并将其定位到人类2号染色体。人类和大鼠尿皮质素在成熟肽区域有95%的同源性。合成的人类尿皮质素能与1型、2α型和2β型CRF受体高亲和力结合，刺激稳定转染这些受体的细胞内cAMP积累，并在体外促使大鼠分散的垂体前叶细胞释放促肾上腺皮质激素（ACTH）。此外，CRF结合蛋白能与人类尿皮质素高亲和力结合，并可在体外阻止尿皮质素刺激的ACTH分泌。CRF结合蛋白对人类尿皮质素的抑制作用可被无生物学活性的CRF片段（如CRF(9 - 33)）阻断。
