SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary.

Gonadotroph pituitary adenomas (GPAs) often present as invasive macroadenomas not amenable to complete surgical resection. Radiotherapy is the only post-operative option for patients with large invasive or recurrent lesions. No medical treatment is available for these patients. The somatostatin analogues (SSAs) octreotide and lanreotide that preferentially target somatostatin receptor type 2 (SSTR2) have little effect on GPAs. It is widely accepted that the expression of specific SSTR subtypes determines the response to SSAs. Given that previous studies on mRNA and protein expression of SSTRs in GPAs generated conflicting results, we investigated the expression of SSTR2, SSTR3 and SSTR5 (the main targets of available SSAs) in a clinically and pathologically well characterized cohort of 108 patients with GPAs. A total of 118 samples were examined by immunohistochemistry using validated and specific monoclonal antibodies. Matched primary and recurrent tissues were available for 10 patients. The results obtained were validated in an independent cohort of 27 GPAs. We observed that SSTR3 was significantly more abundant than SSTR2 (P<0.0001) in GPAs, while full-length SSTR5 was only expressed in few tumors. SSTR3 expression was similar in primary and recurrent adenomas, was high in potentially aggressive lesions and did not significantly change in adenomas that recurred after irradiation. In conclusion, low expression of SSTR2 may account for the limited response of GPAs to octreotide and lanreotide. Given the potent anti-proliferative, pro-apoptotic and anti-angiogenic activities of SSTR3, targeting this receptor with a multireceptor ligand SSA such as pasireotide may be indicated for potentially aggressive GPAs