Gene Expression of Somatostatin Receptor Subtype 2 and 5 in GH-Secreting Pituitary Adenomas / 대한내분비학회지

ABSTRACT

BACKGROUND: SSTR2 and SSTR5 are most frequently observed in GH-secreting pituitary tumors, and SSTR5 is believed to be more specific to mammosomatotroph lineage. Octreotide binds with high affinity to those two types. There is no report that investigates the quantitative comparison of the two subtype gene expressions, and the correlation between their gene expressions and GH response to octreotide in GH-secreting pituitary adenomas. METHOD: GH response to octreotide was examined in 8 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were prepared from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gas gene. mRNAs of SSTR2 and SSTRS were quantitated by the comparative RT-PCR and in vitro transcription. RESULTS: The in vitro transcripts of SSTR2 and SSTR5 cDNA were detected in all tumors. The amount of SSTR transcripts was considerably variable between the tumors. The amount of SSTR5 transcript was significantly smaller than that of SSTR2 transcript (0.07+-0.02 vs. 0.87+-0.10), and they did not show any correlation . There was no signicant difference in sex, age, tumor size and grade, basal GH levels, and the GH responses to octreotide between the group with high and low SSTR gene expression. No significant correlation was found between the GH response to octreotide and the amount of SSTR2 transcript, wherease the amount of SSTR5 transcripts showed a tendency of negative correlation with the octreotide response. Tumors with gsp oncogene showed significantly higher response to octreotide than those without the oncogene. The amount of SSTRS transcript in gsp-positive tumors was significantly smaller than in gsp-negative tumors (0.03+-0.01 vs. 0.12+-0.03). CONCLUSION: These results suggest that SSTRS gene expression is lower than that of SSTR2 in GH-secreting adenomas. It is probably attributed to the binding of somatostatin to SSTR5 which has a higher affinity to the hypothalamic somatostatin, Tumors with gsp-oncogene is likely to express a higher density of SSTR5 than those without the oncogene.