Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas

Abstract

Abstract Context: Previous studies have demonstrated the expression of somatostatin receptor subtypes (mainly sst5) and dopamine (DA) receptor subtypes (mainly D2) in smaller series of human corticotroph adenomas. In line with these findings, sst5 and D2-targeting agents have already been used clinically in patients with Cushing’s disease (CD) and have shown promising results in subsets of patients. To what extent these receptor subtypes are coexpressed within individual adenomas, is not known however. Objective: The aim of the study was to investigate the (co-)expression of both sst and DA receptors in a large series of human corticotroph adenomas. Design: We conducted in vitro analysis of corticotroph adenoma tissue obtained via transsphenoidal adenomectomy. Setting: The study was conducted at two university medical centers. Patients: Thirty patients with CD participated in the study. Results: Analyzed by quantitative RT-PCR, D2 and sst5 were significantly (co-) expressed in the majority (60%) of adenomas, whereas 23% of adenomas only expressed D2, but not sst5. The remaining 17% of adenomas did not significantly express either sst5 or D2. Overall, expression of sst1–4 and D4 was low to nondetectable. Corticotroph adenomas with invasive growth invariably showed loss of sst5 and D2 expression. Autoradiography revealed clear D2 and/or SS-14 binding in a subset of cases, which correlated well with their respective mRNA data. Conclusions: sst5 and especially D2 are highly expressed in the majority of human corticotroph adenomas, with coexpression of sst5 and D2 being a common phenomenon. These findings support the current studies with sst5 and D2-targeting agents in patients with CD and highlight the rationale behind sst5-D2 combination therapy.