Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors

作者：Natalio Vita, Patrick Laurent, Sylvie Lefort, Pascale Chalon, Jean-Michel Lélias, Mourad Kaghad, Gérard Le Fur, Daniel Caput, Pascual Ferrara · 发表于：FEBS Letters · 年份：1993 · DOI：10.1016/0014-5793(93)80427-v · 被引用次数：326 · 研究领域：Stress Responses and Cortisol、Adrenal Hormones and Disorders、Hypothalamic control of reproductive hormones

Corticotrophin-releasing factor (CRF) is the principal hypothalamic factor governing the pituitary-adrenal axis, but the wide extra-pituitary distribution of CRF and its receptors suggest a major role for this neuropeptide in the integration of the overall physiological and behavioral responses of an organism to stress. We have cloned a CRF receptor complementary DNA (cDNA) by expression in COS-7 cells of a cDNA library from the AtT20 mouse pituitary tumour cell line. The cloned mouse cDNA was then as a probe to isolate a human CRF receptor cDNA from a human brain cDNA library. The mouse and human cDNAs both encode 415 amino acid proteins that are 97% identical, containing seven putative transmembrane domains characteristic of G protein-coupled receptors. The CRF receptor shows homology with the receptors for growth hormone-releasing factor, vasoactive intestinal peptide, secretin, parathyroid hormone, and calcitonin. COS-7 cells transfected with the mouse CRF receptor cDNA bind radiolabelled ovine CRF with high affinity and respond specifically to CRF by accumulation of intracellular cAMP. A 2.7 kb mRNA coding for the CRF receptor could be detected in AtT20 cells and human cortex tissue. PCR analysis also detected the receptor transcript in human pituitary, brainstem, and testis.