Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone.
A novel cDNA was isolated from rat pituitary mRNA using the polymerase chain reaction to amplify sequences encoding G protein-coupled receptors. The human homolog of this cDNA was isolated and expressed in human kidney 293 cells, and membrane fractions from these cells were found to bind human GH-releasing hormone (GHRH) with high affinity and specificity. GHRH also stimulates intracellular cAMP production in these transfected cells. The encoded receptor protein contains seven potential membrane-spanning domains, a hallmark of G protein-coupled receptors, and is homologous to previously identified receptors for secretin and vasoactive intestinal peptide, ligands that are related to GHRH. The rat GHRH receptor mRNA is expressed predominantly, if not exclusively, in the anterior pituitary gland, the major target for GHRH action. These results define a mechanism for cellular signaling by GHRH and provide the opportunity to examine the role of the GHRH receptor in growth abnormalities that involve the GH axis.
Mayo
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Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208.
D000236:Adenoma; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007700:Kinetics; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms; D016133:Polymerase Chain Reaction / Q000379:methods; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter / Q000235:genetics* / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D017981:Receptors, Neurotransmitter; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D011994:Recombinant Proteins; D013006:Growth Hormone; D004247:DNA; D000242:Cyclic AMP; C048250:somatotropin releasing hormone receptor