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This Article Full Text Full Text (PDF) All Versions of this Article: JME-08-0110v1 42/1/47    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by de Bruin, C Articles by Hofland, L J Search for Related Content PubMed PubMed Citation Articles by de Bruin, C Articles by Hofland, L J

Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Room Ee569, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

(Correspondence should be addressed to C de Bruin; Email: c.debruin{at}erasmusmc.nl)

Dopamine agonists (DA) and somatostatin (SS) analogues have been proposed in the treatment of ACTH-producing neuro-endocrine tumours that cause Cushing's syndrome. Inversely, glucocorticoids (GCs) can differentially influence DA receptor D₂ or SS receptor subtype (sst) expression in rodent models. If this also occurs in human neuro-endocrine cells, then cortisol-lowering therapy could directly affect the expression of these target receptors. In this study, we investigated the effects of the GC dexamethasone (DEX) on D₂ and sst expression in three human neuro-endocrine cell lines: BON (carcinoid) and TT (medullary thyroid carcinoma) versus DMS (small cell lung cancer), which is severely GC resistant. In BON and TT, sst₂ mRNA was strongly down-regulated in a dose-dependent manner (IC₅₀ 0.84 nM and 0.16 nM), whereas sst₅ and especially D₂ were much more resistant to DEX treatment. Sst₂ down-regulation was abrogated by a GC receptor antagonist and reversible in time upon GC withdrawal. At the protein level, DEX also induced a decrease in the total number of SS (–52%) and sst₂-specific (–42%) binding sites. Pretreatment with DEX abrogated calcitonin inhibition by sst₂-preferring analogue octreotide in TT. In DMS, DEX did not cause significant changes in the expression of these receptor subtypes. In conclusion, we show that GCs selectively down-regulate sst₂, but not D₂ and only to a minor degree sst₅ in human neuro-endocrine BON and TT cells. This mechanism may also be responsible for the low expression of sst₂ in corticotroph adenomas and underwrite the current interest in sst₅ and D₂ as possible therapeutic targets for a medical treatment of Cushing's disease.

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				C. de Bruin, A. M. Pereira, R. A. Feelders, J. A. Romijn, F. Roelfsema, D. M. Sprij-Mooij, M. O. van Aken, A.-J. van der Lelij, W. W. de Herder, S. W. J. Lamberts, et al. Coexpression of Dopamine and Somatostatin Receptor Subtypes in Corticotroph Adenomas J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1118 - 1124. [Abstract] [Full Text] [PDF]