Expression of Somatostatin Receptor (SSTR) Subtypes in Pituitary Adenomas: Quantitative Analysis of SSTR2 mRNA by Reverse Transcription‐Polymerase Chain Reaction

Abstract

The expression of somatostatin receptor (SSTR) subtypes and relative abundance of SSTR2 mRNA were examined in 18 pituitary adenomas using the reverse transcription-polymerase chain reaction (RT-PCR) method. SSTR1 and SSTR2 were expressed in all pituitary adenomas examined. Six of 9 somatotroph adenomas, 1 of 4 lactotroph adenomas and 1 of 2 thyrotroph adenomas also expressed SSTR5. SSTR3 and SSTR4 mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively. SSTR2 mRNA expression was quantified by comparison with the PCR cycle-dependent amplification of beta-actin or cyclophilin. The relative abundance of SSTR2 mRNA varied greatly among adenomas with more than a 1000-fold difference. SSTR2 mRNAs in lactotroph adenomas were less abundant (P < 0.01) than those in somatotroph adenomas. No significant correlation was found between the relative abundance of SSTR2 mRNA levels and GH sensitivity to octreotide administration. However, one of the thyrotroph adenomas exhibited marked shrinkage in tumor size after octreotide therapy, in which SSTR2 mRNA was the most abundant among the adenomas examined. GH sensitivity to octreotide was not significantly different between SSTR5 mRNA positive and negative adenomas. In conclusion, SSTR2 mRNA levels varied greatly among pituitary adenomas but were not correlated with GH sensitivity to octreotide. Further investigations of functional SSTR subtype proteins and of postreceptor signal transductions are required to clarify the molecular mechanisms of octreotide action.

Quantitative analysis of somatostatin receptor subtype (SSTR1–5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas

“…All the five genes are expressed in normal adult human pituitaries, however, SSTR4 mRNA is found at extremely low levels (15,16). Somatostatin receptors expression in pituitary adenomas is reported to be highly variable within and between tumor subtypes (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In studies conducted with non-pituitary tissues, all SSTR subtypes have been shown to have anti-proliferative effects in some cell types and SSTR2 and SSTR3 were specifically shown to initiate apoptosis (34).…”

Preclinical and clinical experiences with the role of somatostatin receptors in the treatment of pituitary adenomas

“…sst 2 and sst 5 receptors are the predominantly expressed sst, both at the mRNA (Table 1; (16)(17)(18)(19)) and the protein level (20). Several studies reported a variable sst 2 mRNA expression and a relatively high expression of sst 5 (16,18,21).…”

Current perspectives on the pathogenesis of clinically non-functioning pituitary tumours

“…The dopamine type 2 receptor gene has also been analysed in a series of NFTs and no mutations were detected (Friedman et al 1994). Differential expression of somatostatin receptor subtypes has been demonstrated in NFTs, although no consistent pattern of subtype expression has been determined (Greenman & Melmed 1994, Miller et al 1995, Panetta & Patel 1995, Murabe et al 1996.…”