Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas

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, sst5and 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 wasto investigatethe (co-)expression of both sst and DA receptors in a large series of human corticotroph adenomas. Design: We performed in vitro analysis of corticotroph adenoma tissue obtained via transsphe- noidal adenomectomy. Setting: The study was conducted at two university medical centers. Patients: Adenoma tissue from 30 patients with CD was analyzed in this study. Results: Analyzed by quantitative RT-PCR, D2and sst5were significantly (co-) expressed in the majority (60%) of adenomas, whereas 23% of adenomas only expressed D5, but not sst5. The remaining 17% of adenomas did not significantly express either sst5or D2. Overall, expression of sst1-4and D4was low to nondetectable. Corticotroph adenomas with invasive growth invariably showed loss of sst5and D2expression. Autoradiography revealed clear D2and/or SS-14 binding in a subset of cases, which correlated well with their respective mRNA data. Conclusions: sst5and especially D2are highly expressed in the majority of human corticotroph adenomas, with coexpression of sst5and D2being a common phenomenon. These findings support the current studies with sst5and D2-targeting agents in patients with CD and highlight the rationale behind sst5-D2combination therapy. Copyright

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