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Absence of somatostatin receptor type 2 A mutations and gip oncogene in pituitary somatotroph adenomas
S Petersenn1, M Heyens, D K Lüdecke
1IHF Institute for Hormone and Fertility Research, University of Hamburg, Hamburg, Germany; Department of Medicine, University Hospital Eppendorf, Hamburg, Germany. petersenn@uke.uni-hamburg.de
Objective:
Somatostatin, acting via specific receptors in the anterior pituitary, tonically inhibits pituitary growth hormone secretion and somatotroph proliferation. Reduction of growth hormone secretion and tumour regression in GH-secreting pituitary adenomas treated with long-acting somatostatin analogues varies widely. In 30-40% of these tumours dominant somatic mutations of the Gsalpha gene (gsp) have been demonstrated leading to constitutive adenylyl cyclase induction. A relationship between somatostatin sensitivity and tumour pathogenesis in some tumours has been suggested. Changes in the function of the somatostatin receptor or intracellular signal elements may be of relevance. Somatostatin receptor type 2 A (sst2A) and Gi2 are proposed to mediate selectively the inhibition of GH release in the somatotroph. We therefore investigated the presence of sst2A mutations and gip oncogene in somatotrophic pituitary adenomas.
Design:
Tumour samples from 15 patients with pituitary somatotroph adenomas were obtained. RNA was isolated and used for reverse transcription and subsequent polymerase chain reaction. All samples were screened for the presence of sst2A mutations and of the gip oncogene by SSCP analysis and sequencing. For comparison, the gsp oncogene was examined. The relationship between clinical data and molecular analysis results was investigated.
Results:
Seven of the tumours harboured a gsp mutation. No mutations affecting the sst2A protein were found in any of the tumours analysed. Furthermore, gip oncogene was absent in all tumours.
Conclusion:
Mutations of the somatostatin receptor type 2 A and the gip oncogene are unlikely to be involved in the pathogenesis of acromegaly.
Insights
Mutations in the somatostatin receptor type 2 A (sst2A) and the gip oncogene were not found in pituitary adenomas, suggesting they do not cause acromegaly. The study focused on growth hormone secretion and tumor pathogenesis.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Somatostatin inhibits pituitary growth hormone (GH) secretion and somatotroph proliferation.
- GH-secreting pituitary adenomas show variable response to somatostatin analogues.
- Gsalpha gene (gsp) mutations are found in 30-40% of these tumors, leading to constitutive adenylyl cyclase induction.
Purpose of the Study:
- To investigate the role of somatostatin receptor type 2 A (sst2A) mutations and the gip oncogene in the pathogenesis of somatotrophic pituitary adenomas.
- To explore potential mechanisms underlying variable somatostatin analogue efficacy in acromegaly treatment.
Main Methods:
- Tumor samples from 15 pituitary somatotroph adenoma patients were analyzed.
- Reverse transcription-polymerase chain reaction, SSCP analysis, and sequencing were used to screen for sst2A mutations and gip oncogene.
- The presence of the gsp oncogene was also examined for comparison.
Main Results:
- No mutations affecting the sst2A protein were detected in any of the analyzed tumors.
- The gip oncogene was absent in all investigated pituitary adenomas.
- Seven out of 15 tumors harbored a gsp mutation.
Conclusions:
- Mutations in the somatostatin receptor type 2 A are unlikely to be involved in acromegaly pathogenesis.
- The gip oncogene does not appear to play a role in the development of somatotrophic pituitary adenomas.
- Further research may be needed to understand the molecular mechanisms of somatostatin analogue resistance.