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

Abstract

Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2OSSTR3[SSTR1\SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (rZ0.51 and rZ0.66; PZ0.05 and PZ0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide. 156 65-74 European Journal of Endocrinology

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

“…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).…”

Overexpression of SSTR2 inhibited the growth of SSTR2-positive tumors via multiple signaling pathways

“…High levels of SSTR2 have been identified in pituitary, pancreatic islet cells, adrenals and thymus. Expression of SSTRs has also been demonstrated in most tumors of neuroendocrine origin whereas they have been found expressed with much lower frequencies in nonendocrine tumors [4,5]. Activation of SSTRs in these SSTR-expressing tumors usually resulted in remarkable inhibition of tumor cell proliferation via both indirect activities of inhibiting growth hormone secretion and direct activity through SSTR signaling pathways [6].…”

Expression of functional KISS1 and KISS1R system is altered in human pituitary adenomas: evidence for apoptotic action of kisspeptin-10

“…This partial or complete loss of expression of the KISS1/KISS1R system in pituitary adenomas suggests that a functional involvement of these genes in the etiology of pituitary tumors should not be discarded, as it has been reported elsewhere for several neuropeptides as galanin, neurotensin, vasopressin, and cholecystokinin (27,28). Likewise, expression levels of somatostatin receptors often show pathophysiologically relevant alterations in pituitary tumors (29), and it will be of interest to analyze the possible relationship between these two inhibitory systems, KISS1/KISS1R and somatostatin/somatostatin receptors, at the pituitary level, especially in GH adenomas. In line with this, although the precise relevance and underlying mechanism of the uneven expression of KISS1/KISS1R in human pituitary adenomas are yet to be elucidated, it is not unreasonable to propose that understanding the impaired expression of this molecular tandem may result, in the future, of therapeutic or clinical relevance in the outcome of patients with pituitary adenomas, as it has been already anticipated in several malignancies, including melanoma (30,31), carcinoma of the ovary (32), stomach (33), urinary bladder (34), and esophagus (35).…”