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Inhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor

DC FieldValueLanguage
dc.contributor.author이은직-
dc.date.accessioned2016-05-16T11:09:43Z-
dc.date.available2016-05-16T11:09:43Z-
dc.date.issued2002-
dc.identifier.issn0022-0795-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/143927-
dc.description.abstractGH3 rat pituitary tumor cells produce GH and prolactin (PRL), but lack the GHRH receptor (GHRH-R). We expressed human GHRH-R (hGHRH-R) in GH3 cells using recombinant adenoviral vectors and studied the effects of GHRH antagonists. The mRNA expression of the GHRH-R gene in the cells was demonstrated by RT-PCR. An exposure of the GH3 cells infected with hGHRH-R to 10(-10), 10(-9) and 10(-8) m hGHRH for 1 or 2 h in culture caused a dose-dependent elevation of the intracellular cAMP concentration and the cAMP efflux. Exposure to hGHRH also elicited dose-dependent increases in GH and PRL secretion from these cells. Neither the uninfected nor the antisense hGHRH-R-infected control cells exhibited cAMP, GH and PRL responses to GHRH stimulation. GHRH antagonists JV-1-38 and jv-1-36 applied at 3x10(-8) m for 3 h, together with 10(-9) m GHRH, significantly inhibited the GHRH-stimulated cAMP efflux from the hGHRH-R-infected cells by 36 and 80% respectively. The more potent antagonist JV-1-36 also decreased the intracellular cAMP levels in these cells by 55%. Exposure to JV-1-36 for 1 h nullified the stimulatory effect of GHRH on GH secretion and significantly inhibited it by 64 and 77% after 2 and 3 h respectively. In a superfusion system, GHRH at 10(-10), 10(-9) and 10(-8) m concentrations induced prompt and dose-related high cAMP responses and smaller increases in the spontaneous GH secretion of the hGHRH-R-infected cells. Antagonists JV-1-36 and JV-1-38 applied at 3x10(-8) m for 15 min, together with 10(-9) m GHRH, inhibited the GHRH-stimulated cAMP response by 59 and 35% respectively. This work demonstrates that GHRH antagonists can effectively inhibit the actions of GHRH on the hGHRH-R. Our results support the view that this class of compounds would be active clinically.-
dc.description.statementOfResponsibilityopen-
dc.format.extent425~434-
dc.relation.isPartOfJOURNAL OF ENDOCRINOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCyclic AMP/analysis-
dc.subject.MESHCyclic AMP/biosynthesis-
dc.subject.MESHGene Expression/genetics-
dc.subject.MESHGrowth Hormone/analysis-
dc.subject.MESHGrowth Hormone/metabolism-
dc.subject.MESHGrowth Hormone-Releasing Hormone/analogs & derivatives*-
dc.subject.MESHGrowth Hormone-Releasing Hormone/antagonists & inhibitors-
dc.subject.MESHGrowth Hormone-Releasing Hormone/genetics-
dc.subject.MESHHumans-
dc.subject.MESHPituitary Gland/cytology-
dc.subject.MESHPituitary Gland/physiology*-
dc.subject.MESHProlactin/analysis-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRats-
dc.subject.MESHReceptors, Somatotropin/genetics*-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHTumor Cells, Cultured-
dc.titleInhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorM Kovacs-
dc.contributor.googleauthorAV Schally-
dc.contributor.googleauthorEJ Lee-
dc.contributor.googleauthorR Busto-
dc.contributor.googleauthorP Armatis-
dc.contributor.googleauthorK Groot-
dc.contributor.googleauthorJL Varga-
dc.identifier.doi10.1677/joe.0.1750425-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03050-
dc.relation.journalcodeJ01392-
dc.identifier.eissn1479-6805-
dc.identifier.pmid12429040-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.rights.accessRightsfree-
dc.citation.volume175-
dc.citation.number2-
dc.citation.startPage425-
dc.citation.endPage434-
dc.identifier.bibliographicCitationJOURNAL OF ENDOCRINOLOGY, Vol.175(2) : 425-434, 2002-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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