Endocrine Abstracts

Introduction: Somatostatin analogs (SSAs) are the first-line clinical treatment for patients with pituitary adenomas (PAs) but their efficacy is highly variable among patients. This could be due to a differential expression of somatostatin receptor subtypes (Ssts) among tumors, but this issue is still unresolved. Nonfunctioning pituitary adenomas (NFPAs), which mostly derive from gonadotroph cells, are among the tumors that poorly respond to SSAs. Rats carrying a germline loss-of-function mutation in p27 (MENX syndrome) develop gondotroph adenomas that closely resemble human gonadotroph tumors. To determine whether rat PAs can be used to explore the relationship between Sst expression and response to SSA, we determined the expression profile of Ssts in these tumors and assessed their response in vitro to the SSA octreotide.

Methods: Adenoma tissues or primary PA cells from MENX-affected rats were used. qRT-PCR, immunohistochemistry (IHC) and in vitro autoradiography were performed to determine Ssts expression. Rat primary PA cells were treated with the octreotide and cell viability assessed. Small animal positron emission tomography (PET) was performed using the somatostatin agonist 68Ga-DOTA-NOC.

Results: We observed higher expression of Sst2 and Sst3 mRNA in PA cells from mutant rats when compared with cells from wild-type rats. Accordingly, Sst2 protein was found more highly expressed in the rat tumors (especially the small ones) than in non-tumorous pituitary areas by IHC. Sst3 protein was also detectable in the rat tumors. Treatment of rat primary PA cells in vitro with octreotide showed that they partially respond to the drug, similarly to human NFPAs. By 68Ga-DOTA-NOC-PET imaging, we found the increased uptake in the pituitaries of mutant rats in vivo when compared with wild-type rats.

Conclusion: Studies of MENX-associated PAs might help us understand the relationship between Sst expression and response to SSAs in NFPA.