Absence of somatostatin receptor type 2 A mutations and gip oncogene in pituitary somatotroph adenomas

OBJECTIVE Somatostatin, acting via specific receptors in the anterior pitui tary, 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 a nalogues varies widely. In 30-40% of these tumours dominant somatic mutatio ns of the G(s)alpha gene (gsp) have been demonstrated leading to constituti ve adenylyl cyclase induction. A relationship between somatostatin sensitiv ity 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 G(i2) are p roposed to mediate selectively the inhibition of GH release in the somatotr oph. We therefore investigated the presence of sst2A mutations and gip onco gene 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 subs equent polymerase chain reaction. All samples were screened for the presenc e of sst2A mutations and of the gip oncogene by SSCP analysis and sequencin g. 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 affecti ng 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 onco gene are unlikely to be involved in the pathogenesis of acromegaly.