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Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas

Department of Internal Medicine (C.d.B., R.A.F., D.M.S.-M., M.O.v.A., A.-J.v.d.L., W.W.d.H., S.W.J.L., L.J.H.), Division of Endocrinology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands; and Department of Endocrinology and Metabolism (A.M.P., J.A.R., F.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: C. de Bruin, M.D., Department of Internal Medicine, Room Ee569, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. E-mail: c.debruin{at}erasmusmc.nl.

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 performed in vitro analysis of corticotroph adenoma tissue obtained via transsphenoidal 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, 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 sst_1–4 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.