Somatostatin receptor subtype 2 and 5 in human GH‐secreting pituitary adenomas: analysis of gene sequence and mRNA expression

Abstract

The role of somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) in determining the secretory and proliferative phenotype as well as the sensitivity to somatostatin analogue treatment is not clearly established. We quantified the expression of SSTR2 and SSTR5 mRNA using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 19 human growth hormone (GH) -secreting adenomas. Tumour characteristics and in vivo sensitivity to somatostatin analogues were assessed; tumours were screened for Gsalpha gene mutations. PCR products of SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were directly sequenced. All tumours expressed both SSTR2 and SSTR5 mRNA at variable levels. No significant correlation between SSTR2 and SSTR5 expression and the presence of Gsalpha mutation, GH levels, or tumour size and invasiveness was observed. A negative correlation between SSTR2 and SSTR5 mRNA levels was observed (r = 0.5; P < 0.05). No significant correlation between the levels of SSTR2 and SSTR5 expression and the in vivo responsiveness to somatostatin analogues was observed, although a tendency to a low SSTR2 expression in resistant tumours was found. No mutations in the coding or bordering regions of either SSTR2 or SSTR5 adenomatous DNA from patients totally or partially resistant to somatostatin analogues were found. The study shows that the different expression of SSTR2 and SSTR5 in GH-secreting adenomas is not significantly correlated with the secretory and proliferative phenotype, although the large, hypersecretory tumours and those with a poor sensitivity to somatostatin analogues seem to express low levels of SSTR2 mRNA. Moreover, both SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were found to possess intact coding sequences.

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

“…We report that SSTR2 mRNA levels positively correlate with the percentage GH and IGF-I reduction, as well as the percentage of tumor volume reduction, up to 6 months of treatment with OCT LAR. The finding that patients whose tumors express higher SSTR2 mRNA levels tend to respond better to OCT LAR therapy in terms of hormonal control is consistent with preliminary data reported by our group in a subset of these patients (19) and reports by others (20)(21)(22)(23). On the other hand, it is important to note that other factors such as initial GH levels (5) may also influence tumor responsiveness to OCT LAR therapy.…”

“…Consistent with this, several authors have described that patients bearing tumors with the highest SSTR2 expression respond better to SA treatment in terms of hormonal control (19)(20)(21)23). Some groups have also studied the in vitro anti-proliferative action of SA and its correlation with the tumor SSTR expression pattern (26)(27)(28).…”

“…When molecular analysis of the resected tumor is possible, the presence of the gsp oncogene is indicative of a good response to SA treatment (18). In addition, expression profiles of the somatostatin receptor subtypes (SSTR) in tumor fragments may serve as a predictive tool of response to SA therapy, although further study is required (19)(20)(21)(22)(23)(24).…”

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

“…Despite the fact that most studies suggest that gsp-positive adenomas respond better to octreotide LAR ® compared to gsp-negative tumors, a recent study failed to fi nd differences in octreotide LAR ® sensitivity according to gsp status (18). In addition, expression profi les of the mRNA somatostatin receptor subtypes (SSTR) in tumor fragments may serve as a predictive tool of biochemical and tumor volume response to SA therapy (24,(27)(28)(29)(30)(31)(32).…”

Estudo molecular dos genes GNAS, PTTG, AIP, CDKN1B e MEG3 em adenomas hipofisários esporádicos

“…Na maioria dos estudos, a presença de gsp + em adenomas GH tem uma prevalência de aproximadamente 40% (53)(54)(55)(56)(57)(58)(59)(60). No presente estudo a prevalência de gsp + em adenomas GH foi de 27%, resultado similar a outros estudos descritos (63,144) Recentemente um estudo demonstrou pela primeira vez uma correlação genótipo-fenótipo com a síndrome NEM1 no qual a variante p.V109G influencia na manifestação clínica de pacientes adultos NEM1 portadores de mutações truncadas no gene MEN1 (170). Não há na literatura correlações deste polimorfismo com adenomas hipofisários esporádicos.…”