J Korean Soc Endocrinol.  2002 Apr;17(2):158-169.

Gene Expression of Somatostatin Receptor (Subtype 2 & 5), Gi2 alpha and Pit-1 in GH-secreting Pituitary Adenomas

Affiliations
  • 1Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, Korea.
  • 2Endocrine Research Institute, Kyunghee University School of Medicine, Seoul, Korea.
  • 3Department of Pharmacology, Kyunghee University School of Medicine, Seoul, Korea.
  • 4Department of Neurosurgery, Kyunghee University School of Medicine, Seoul, Korea.

Abstract

BACKGROUND: Mutation of Gs protein subunit (gsp oncogene), detected in about 30~40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for Gi2 alpha , Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2 alpha, Pit-1 and sst (2&5) in GH-secreting pituitary tumors.
METHODS
The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted 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 Gs gene. Sst2, sst5, Gi2 alpha and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR.
RESULTS
Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, Gi2 alpha mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-).
CONCLUSION
These data suggests that gsp oncogene may increase Gi2 alpha levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the Gi2 alpha gene might be an inhibitory compensatory response to the action of gsp oncogene.


MeSH Terms

Acromegaly
Clinical Coding
Codon
DNA
Exons
Gene Expression*
Growth Hormone
Growth Hormone-Secreting Pituitary Adenoma*
Humans
Octreotide
Oncogenes
Pituitary Neoplasms
Polymerase Chain Reaction
Protein Subunits
Receptors, Somatostatin*
RNA
RNA, Messenger
Somatostatin*
Somatotrophs
Codon
DNA
Growth Hormone
Octreotide
Protein Subunits
RNA
RNA, Messenger
Receptors, Somatostatin
Somatostatin
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