Role of dopamine receptors in normal and tumoral pituitary corticotropic cells and adrenal cells

Mara Boschetti, Federico Gatto, Marica Arvigo, Daniela Esposito, Alberto Rebora, Miryam Talco, Manuela Albertelli, Elena Nazzari, Umberto Goglia, Francesco Minuto, Diego Ferone

Research output: Contribution to journalArticlepeer-review

Abstract

The recent depiction of dopamine receptors (DRs) in tumors that cause Cushing's syndrome (CS) has renewed the debate about the dopamine control on pituitary-adrenal axis, and opened interesting new perspectives for medical treatment of CS. The new insights arise from the recent accurate characterization of DR subtypes expression within tumors causing CS, the discovery of new mechanisms, such as the dimerization between DRs and other G-protein coupled receptors (CPCRs), including somatostatin receptors (SSTRs), and the recent availability of new agents targeting these receptor subtypes. Corticotropic adenomas express DR subtype 2 (D2R), together with different SSTR subtypes (ssts), in particular sst5. In vitro, activation of D2R inhibits ACTH release in the majority of cultures of corticotropic cells, whereas, in vivo, dopaminergic agents display an inhibitory effect on cortisol levels in a subset of patients with CS. In animal models the receptor profile can be deeply modulated in specific environmental conditions, that may resemble the different clinical phases of CS. The new insights about DRs and receptor-targeting drugs may offer different approaches for medical treatment of CS: combination therapies with different types of compounds, treatment with novel molecules (hybrid compounds) with a wider spectrum of activity, or even pretreatment manipulation of receptor profile. Finally, recent studies showed that D2R is also significantly expressed in ectopic ACTH-secreting tumors and in both normal and tumoral adrenal tissues. Dopamine-agonists may decrease cortisol levels in a number of these patients, strengthening the current (re)emerging interest in DRs as possible targets for medical treatment of CS.

Original languageEnglish
Pages (from-to)17-22
Number of pages6
JournalNeuroendocrinology
Volume92
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Sep 2010

Keywords

  • Adrenal
  • Adrenal carcinoma
  • Chimeric molecules
  • Cushing's syndrome
  • Dopamine receptors
  • Hypercortisolism
  • Pituitary

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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