Relevance of coexpression of somatostatin and dopamine D2 receptors in pituitary adenomas.
Dopamine and somatostatin are both involved in the negative control of normal pituitary cells. Dopamine subtype 2 receptor (D2DR) and somatostatin receptor (sst) agonists, mainly directed to sst2, are used in the treatment of pituitary adenomas. Nevertheless, a majority of corticotroph and gonadotroph adenomas and a third of somatotroph adenomas are still not sufficiently controlled by these treatments. D2DR and sst1, 2, 3 and 5 are present in most pituitary adenomas. These receptors may interact by heterodimerization as shown for sst1-sst5, sst5-D2DR, sst2-sst3 and sst2-D2DR suggesting possible additive effects. D2DR and sst2 agonist cotreatment showed limited additivity on GH secretion in acromegaly. Moreover, new chimeric compounds with sst2, D2DR and sst5 affinity have shown an increased control of secretion and/or proliferation of different types of pituitary adenomas in cell culture. Together with the multi-sst ligand drugs recently developed, these dopamine-somatostatin ligands represent a new opportunity in the combinatory treatment of pituitary adenomas.
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Laboratory Interactions Cellulaires Neuroendocriniennes, UMR 6544 CNRS, Institut Fédératif Jean Roche, Faculté de Médecine Nord, Université de la Méditerranée, Marseille, France. alexandru.saveanu@univmed.fr
Jaquet
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Barlier
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D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000077465:Cabergoline; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004873:Ergolines / Q000627:therapeutic use; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D015282:Octreotide / Q000627:therapeutic use; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D055503:Protein Multimerization; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D004873:Ergolines; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; D000077465:Cabergoline; D015282:Octreotide; D004298:Dopamine