Presence of growth hormone secretagogue receptor messenger ribonucleic acidin human pituitary tumors and rat GH3 cells.
Journal Title: Journal of Clinical Endocrinology and Metabolism - Year 1998, Vol 83, Issue 2
Abstract
A novel G11-protein-coupled receptor specific for synthetic GH-releasingpeptides (GHRPs) has recently been cloned and sequenced. Two forms exist, types 1a and 1b, the latterof which is biologically inactive. Using RT-PCR, we looked for the presence in tumorous pituitary cellsof messenger ribonucleic acid (mRNA) for this novel GH secretagogue receptor (GHS-R). Both subtypes ofGHS-R mRNA were detected in all six human pituitary somatotropinomas removed from patients with acromegaly.In culture, four of the tumors exhibited strong responses to GHRP-2 in terms of both phosphatidylinositol(PI) hydrolysis and GH secretion, but two were resistant. There was no apparent difference in the type1a and type 1b expression pattern, as judged by RT-PCR, between responsive and nonresponsive tumors.Similarly, the rat pituitary tumor cell line, GH3, was found to express GHS-R mRNA, although these cellsalso did not respond to GHRPs. RT-PCR failed to detect GHS-R mRNA in eight functionless human pituitarytumors. In contrast, prolactinomas were found to express the receptor and, in culture, significant stimulationof PRL secretion and PI hydrolysis occurred in two of three tumors tested. These results demonstratethat tumorous somatotrophs express the GHS-R gene and that the occasionally observed nonresponsivenessof somatotropinomas to GHRPs is not due to the absence of the biologically active type 1a receptor. Additionally,human pituitary prolactinomas also express GHS-R and are able to respond to GHRPs in terms of PI hydrolysisand PRL secretion. In contrast, GHS-R gene expression does not appear to be associated with human functionlesspituitary tumors.
Authors and Affiliations
E F Adams, B Huang, M Buchfelder, A Howard, R G Smith, S D Feighner, L H van der Ploeg, C Y Bowers, R Fahlbusch
Keywords
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