Expression of Type 5 Somatostatin Receptor in TSH-secreting Pituitary Adenomas: A Possible Marker for Predicting Long-term Response to Octreotide Therapy

Abstract

Abstract. In TSH-secreting pituitary adenomas (TSHoma), octreotide (OCT) therapy reduces tumor size and TSH secretion in some cases but not in others. As OCT acts through various types of somatostatin receptors (SSTRs), the different responses of TSHoma to OCT might be explained by the differences of SSTR expression. We therefore studied the expression of subtype-specific SSTR mRNA transcripts in tumor tissues by RT-PCR. Type 2 (SSTR2) mRNA transcripts were detected in all 8 tumors but those of SSTR3 and SSTR5 were demonstrated only in 5 of them. Serum TSH levels were decreased by OCT administration test in all patients but OCT therapy was effective in two patients out of three. SSTR5 mRNA was detected in two tumors from the responder, but not in one tumor that was resistant to OCT. These observations suggest that the temporal decrease of TSH by OCT may be mediated by SSTR2, and that the long term response to OCT therapy may be related with the expression of SSTR5. Therefore, the expression of SSTR5 in TSHoma may be a useful marker for predicting the outcome of the therapy, but further studies with larger numbers of patients are necessary.

In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5

“…This observation finds a molecular correlate in the previously reported functional data suggesting that SSTR5 expression influences SSTR2 internalization [24]. Moreover, the lack of SSTR5 expression has been considered the reason for the resistance to octreotide treatment and progression of tumor growth in another case of TSHoma [9]. These findings appear in line with a case of octreotide-resistant TSHoma and loss of heterozygosity at the SSTR5 locus, displaying an unusual tumor aggressiveness, which required adjuvant surgery [25].…”

“…Left panels, coronal sections; right panels, sagittal sections mechanism behind the heterogeneity of TSHoma response has not been understood yet. A recent in vivo study, analyzing two TSHoma cases, suggested that SSTR5 expression on top of SSTR2 might account for the longterm suppression of hormonal hypersecretion [9]. This observation finds a molecular correlate in the previously reported functional data suggesting that SSTR5 expression influences SSTR2 internalization [24].…”

“…Recently, a correlation between SSTR2-mediated inhibition of TSH secretion and the consistent expression of SSTR5 on cell membrane has been reported in few cases of TSH-secreting adenomas [9,10].…”

Somatostatin Receptor Subtypes mRNA in TSH-Secreting Pituitary Adenomas: A Case Showing a Dramatic Reduction in Tumor Size During Short Octreotide Treatment

“…During the revision of this manuscript, similar results were reported by Yoshihara A et al showing the importance of sstr5 mRNA expression for the response to octreotide treatment [32]. This work was supported in part by a research grant from Health and Labor Sciences Research Grants, Research on Measures for Intractable Disease, Hypothalamo-Pituitary Dysfunction Research Group (to Masatomo Mori).…”

AIP and the somatostatin system in pituitary tumours

“…In the case of somatotrophinomas, SSAs aimed at SSTR2 are commonly used in the pre-and post-surgical treatment to decrease GH and insulin-like growth factor 1 (IGF1) secretion and tumour size (Melmed 2009, Melmed et al 2015, Puig Domingo 2015. Additionally, thyrotroph tumours display SSTR2, SSTR3 and SSTR5 (Yoshihara et al 2007, Gatto et al 2012 and octreotide is successfully used to treat these tumours, normalizing TSH levels and decreasing tumour size (Caron et al 2001, Gatto et al 2012, van Varsseveld et al 2014.…”