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Absence of Constitutively Activating Mutations in the GHRH Receptor in GH-Producing Pituitary Tumors

DC FieldValueLanguage
dc.contributor.author이은직-
dc.contributor.author임승길-
dc.date.accessioned2016-02-19T10:56:39Z-
dc.date.available2016-02-19T10:56:39Z-
dc.date.issued2001-
dc.identifier.issn0021-972X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/142046-
dc.description.abstractThe molecular events leading to the development of GH-producing pituitary tumors remain largely unknown. We hypothesized that activating mutations of the GHRH receptor might occur in a subset of GH-producing pituitary tumors. Genomic DNA samples from 54 GH-producing pituitary tumor tissues were screened for mutations of the GHRH receptor. Eleven homozygous or heterozygous nucleotide substitutions [169G > A (A57T), 338C > T (P113L), 363G > T (E121D), 409C > T (H137Y), 547G > A (D183N), 673G > A (V225I), 749G > A (W250X), 760G > A (V254M), 785G > A (S262N), 880G > A (G294R), 1268G > A (C423Y)] were found in 12 patients (22.2%). The 169G > A substitution (A57T) appears to be a polymorphism (4 patients, 7.4%). E121D and V225I were each found in 2 patients. In 1 patient with the V225I sequence, the substitution was not found in genomic DNA from peripheral leukocytes, suggesting a somatic mutation. A patient with a heterozygous W250X mutation was homozygous for the C423Y substitution. These variant GHRH receptors were studied in transfected TSA-201 cells to evaluate the functional consequences of the amino acid changes. None of the GHRH receptor variants was associated with basal elevation of intracellular cAMP. GHRH induced variable cAMP responses. With the W250X and G294R variants, there was no cAMP stimulation by GHRH, indicating that the mutations are inactivating. Expression of the W250X GHRH receptor on the cell membrane was severely decreased and GHRH binding to the G294R GHRH receptor was impaired. Although GHRH receptor variants are common in GH- producing pituitary adenomas, constitutively activating mutations, as a mechanism for GH-producing pituitary tumors appear to be rare.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAmino Acid Sequence-
dc.subject.MESHAmino Acid Substitution-
dc.subject.MESHBase Sequence-
dc.subject.MESHBinding Sites-
dc.subject.MESHCell Line-
dc.subject.MESHCell Membrane/physiology-
dc.subject.MESHCyclic AMP/metabolism-
dc.subject.MESHDNA Primers-
dc.subject.MESHExons-
dc.subject.MESHGenetic Variation-
dc.subject.MESHHeterozygote-
dc.subject.MESHHomozygote-
dc.subject.MESHHuman Growth Hormone/metabolism*-
dc.subject.MESHHumans-
dc.subject.MESHModels, Molecular-
dc.subject.MESHMolecular Sequence Data-
dc.subject.MESHMutation*-
dc.subject.MESHPituitary Neoplasms/genetics*-
dc.subject.MESHPituitary Neoplasms/metabolism-
dc.subject.MESHPituitary Neoplasms/pathology-
dc.subject.MESHPoint Mutation-
dc.subject.MESHPolymorphism, Single Nucleotide-
dc.subject.MESHProtein Structure, Secondary-
dc.subject.MESHReceptors, Neuropeptide/chemistry-
dc.subject.MESHReceptors, Neuropeptide/genetics*-
dc.subject.MESHReceptors, Neuropeptide/physiology-
dc.subject.MESHReceptors, Pituitary Hormone-Regulating Hormone/chemistry-
dc.subject.MESHReceptors, Pituitary Hormone-Regulating Hormone/genetics*-
dc.subject.MESHReceptors, Pituitary Hormone-Regulating Hormone/physiology-
dc.subject.MESHRecombinant Proteins/biosynthesis-
dc.subject.MESHRecombinant Proteins/chemistry-
dc.subject.MESHRecombinant Proteins/metabolism-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.titleAbsence of Constitutively Activating Mutations in the GHRH Receptor in GH-Producing Pituitary Tumors-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorTom J. Kotlar-
dc.contributor.googleauthorIvan Ciric-
dc.contributor.googleauthorMi Kyung Lee-
dc.contributor.googleauthorSung Kil Lim-
dc.contributor.googleauthorHyun Chul Lee-
dc.contributor.googleauthorKap Bum Huh-
dc.contributor.googleauthorKelly E. Mayo-
dc.contributor.googleauthorJ. Larry Jameson-
dc.identifier.doi10.1210/jcem.86.8.7732-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03050-
dc.contributor.localIdA03375-
dc.relation.journalcodeJ01318-
dc.identifier.eissn1945-7197-
dc.identifier.pmid11502843-
dc.identifier.urlhttps://academic.oup.com/jcem/article/86/8/3989/2849123-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.alternativeNameLim, Sung Kil-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.contributor.affiliatedAuthorLim, Sung Kil-
dc.rights.accessRightsnot free-
dc.citation.volume86-
dc.citation.number8-
dc.citation.startPage3989-
dc.citation.endPage3995-
dc.identifier.bibliographicCitationJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol.86(8) : 3989-3995, 2001-
dc.identifier.rimsid31558-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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