Cited 10 times in
Inhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor
DC Field | Value | Language |
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dc.contributor.author | 이은직 | - |
dc.date.accessioned | 2016-05-16T11:09:43Z | - |
dc.date.available | 2016-05-16T11:09:43Z | - |
dc.date.issued | 2002 | - |
dc.identifier.issn | 0022-0795 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/143927 | - |
dc.description.abstract | GH3 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.statementOfResponsibility | open | - |
dc.format.extent | 425~434 | - |
dc.relation.isPartOf | JOURNAL OF ENDOCRINOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cyclic AMP/analysis | - |
dc.subject.MESH | Cyclic AMP/biosynthesis | - |
dc.subject.MESH | Gene Expression/genetics | - |
dc.subject.MESH | Growth Hormone/analysis | - |
dc.subject.MESH | Growth Hormone/metabolism | - |
dc.subject.MESH | Growth Hormone-Releasing Hormone/analogs & derivatives* | - |
dc.subject.MESH | Growth Hormone-Releasing Hormone/antagonists & inhibitors | - |
dc.subject.MESH | Growth Hormone-Releasing Hormone/genetics | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Pituitary Gland/cytology | - |
dc.subject.MESH | Pituitary Gland/physiology* | - |
dc.subject.MESH | Prolactin/analysis | - |
dc.subject.MESH | RNA, Messenger/genetics | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Receptors, Somatotropin/genetics* | - |
dc.subject.MESH | Reverse Transcriptase Polymerase Chain Reaction | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.title | Inhibitory effects of antagonistic analogs of GHRH on GH3 pituitary cells overexpressing the human GHRH receptor | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | M Kovacs | - |
dc.contributor.googleauthor | AV Schally | - |
dc.contributor.googleauthor | EJ Lee | - |
dc.contributor.googleauthor | R Busto | - |
dc.contributor.googleauthor | P Armatis | - |
dc.contributor.googleauthor | K Groot | - |
dc.contributor.googleauthor | JL Varga | - |
dc.identifier.doi | 10.1677/joe.0.1750425 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03050 | - |
dc.relation.journalcode | J01392 | - |
dc.identifier.eissn | 1479-6805 | - |
dc.identifier.pmid | 12429040 | - |
dc.contributor.alternativeName | Lee, Eun Jig | - |
dc.contributor.affiliatedAuthor | Lee, Eun Jig | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 175 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 425 | - |
dc.citation.endPage | 434 | - |
dc.identifier.bibliographicCitation | JOURNAL OF ENDOCRINOLOGY, Vol.175(2) : 425-434, 2002 | - |
dc.identifier.rimsid | 39515 | - |
dc.type.rims | ART | - |
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