title: Effect of 9-cis retinoic acid on dopamine D2 receptor expression in pituitary adenoma cells.
abstract: The dopamine receptor subtype 2 (D2R) promoter contains a functional retinoic acid response element involved in the control of D2R expression. The aim of the study was to evaluate the effect of 9-cis retinoic acid (9-cis RA) on D2R protein expression in human pituitary adenomas and GH3 cell line. Treatment with 9-cis RA (100 nM for 48 hrs) caused a 109 +/- 32% increase of basal D2R levels in five of eight growth hormone (GH)-secreting adenomas (GH-omas), a 129 +/- 28% increase in 7 of 11 nonfunctioning adenomas, and no effect in two resistant prolactinomas by Western blotting. The lack of D2R induction in some tumors was not associated with a different pattern of retinoid x receptor (RXR) and retinoic acid receptor (RAR) isoform expression that was similar in all tumors by immunohistochemistry. While the induction of D2R did not affect the slight but significant inhibitory effect exerted by dopamine (10 nM) on in vitro GH release by GH-oma cultured cells, in pituitary GH3 cell lines cis-9 RA enhanced the dopamine-induced inhibition of in vitro GH release (% inhibition: 16 +/- 2 versus 26 +/- 5, P < 0.05), cell proliferation (25 +/- 2% versus 44 +/- 5%, P < 0.05) and cell viability (16 +/- 0.8% versus 29 +/- 1%, P < 0.05), likely by activating caspase-3 (28 +/- 3% versus basal, P < 0.05). In conclusion, this study provides novel evidence for a permissive role of retinoids on the expression of D2R in a good proportion of pituitary tumors and on the generation of pro-apoptotic signals in GH3 cell line.
authors: Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione Ospedale Maggiore IRCCS, 20122 Milan, Italy.
authors: Sara
authors: S
authors: Bondioni
authors: Anita R
authors: AR
authors: Angioni
authors: Sabrina
authors: S
authors: Corbetta
authors: Marco
authors: M
authors: Locatelli
authors: Stefano
authors: S
authors: Ferrero
authors: Emanuele
authors: E
authors: Ferrante
authors: Giovanna
authors: G
authors: Mantovani
authors: Luca
authors: L
authors: Olgiati
authors: Paolo
authors: P
authors: Beck-Peccoz
authors: Anna
authors: A
authors: Spada
authors: Andrea G
authors: AG
authors: Lania
mesh_terms: D000077556:Alitretinoin; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D017448:Receptors, Dopamine D2; D018168:Receptors, Retinoic Acid; D000077556:Alitretinoin; D014212:Tretinoin; D004298:Dopamine