- Effect of Gs alpha Gene Mutation on the Expression of the Rat Somatostatin Receptor Gene.
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I M Yang, S J Park, H G Jhang, G J Lee, S J Oh, S W Kim, J W Kim, Y S Kim, Y K Choi
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J Korean Endocr Soc. 1999;14(4):657-666. Published online January 1, 2001
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 Abstract
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- BACKGROUND
The growth hormone (GH)-secreting pituitary adenoma with mutation of Gs alpha gene (gsp oncogene) is known to show a higher response to somatostatin. The mechanism for the higher response is unclear. We previously demonstrated that transcription of the rat somatostatin receptor (SSTR) gene was increased by cAMP. Therefore, we investigated whether the mutation of Gs alpha gene can increase SSTR gene expression. METHODS: The mutant Gs alpha expressing plasmid of which arginine of codon 201was replaced with histidine was transfected transiently and permanently into GH3 cells. cAMP and rat GH were measured by radioimmunoassay. mRNA expression of the rat SSTR2 was determined by a semiquantitative RT-PCR. RESULTS: The intracellular cAMP production was increased by 1.8 folds in the transiently transfected cells and by 1.5 folds in permanently transfected cells compared to those in the cells transfected with the vehicle plasmid, plasmid expressing the wild type or the plasmid expressing the silent mutant of codon 226. The transcriptional activation by cAMP response element of somatostatin.gene was also increased by 2 folds 24 hours after transient transfection and by 3.5 folds in the permanently transfected cells. The transcriptional activation was not enhanced by forskolin in the transiently transfected cells, whereas it was more remarkably inhibited by somatostatin compared to that in the other transfected cells. The expression of SSTR2 was increased by 1.8 folds 24 hours after transfection in the transiently transfected cells and by 3 folds in the permanently transfected cells, and it was not enhanced by forskolin and isobutylmethylxanthine. The secretion of GH from the transiently transfected cells was not significantly higher than that from the wild type-expressing cells, but it was higher in the permanently transfected cells. The suppression of GH by somatostatin was more prominent in the permanently transfected cells compared to the other transfected cells. CONCLUSION: This study suggests that a higher expression of SSTR induced by the mutant Gs alpha may be a mechanism by which gsp-positive adenomas showed a higher response to somatostatin.
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