title: Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas.
abstract: Recently, it was demonstrated that somatostatin analogs preferential for the SSTR5 subtype suppress PRL release from prolactinoma cell cultures by 30-40%. These data supported the idea of somatostatin receptor subtype-specific control of PRL secretion in such tumors. The present study examines the quantitative profile of SSTRs messenger ribonucleic acid (mRNA) in 10 PRL-secreting tumors and correlates the expression with the ability of native somatostatins (SS14 and SS28), SSTR2 preferential analogs (octreotide and BIM-23197), and the SSTR5 preferential analog BIM-23268 to suppress PRL secretion. RT-PCR quantitative analysis showed a large predominance of SSTR5 mRNA [5648 +/- 1918 pg/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] vs. SSTR2 mRNA (148 +/- 83 pg/pg GAPDH). The SSTR1 transcript was also highly expressed in prolactinomas (1296 +/- 669 pg/pg GAPDH). SSTR5 mRNA expression correlated with PRL inhibition induced by both SRIF14 and SRIF28. Among the different analogs tested, only BIM-23268 produced inhibition of PRL release similar to that achieved with the native peptides. Its EC50 for PRL suppression was 0.28 +/- 0.10 nmol/L. No additive effects on PRL suppression were achieved by cotreatment of the tumor cells with SSTR2 and SSTR5 preferential analogs. In the same tumor cell cultures, quinagolide, a potent dopamine agonist, produced a dose-dependent inhibition of PRL with an EC50 at least 10 times lower than that of BIM-23268. Coincubation of quinagolide and BIM-23268, particularly in tumor cells resistant to dopamine agonist treatment, did not produce additive effects on PRL suppression. In conclusion, prolactinomas have a specific pattern of SSTR subtype mRNA expression (SSTR5 and SSTR1). SSTR5 expression is correlated to PRL regulation. These inhibitory effects are superimposable, at a higher concentration, to those of the dopamine agonists, but are not additive, particularly in the adenomas resistant to dopaminergic suppression of PRL release.
authors.affiliation: Interactions Cellulaires en Neuroendocrinologie, Unite Mixte de Recherche, UMR 6544, Centre National de la Recherche Scientifique, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Jaquet
authors.forename: L
authors.initials: L
authors.lastname: Ouafik
authors.forename: A
authors.initials: A
authors.lastname: Saveanu
authors.forename: G
authors.initials: G
authors.lastname: Gunz
authors.forename: F
authors.initials: F
authors.lastname: Fina
authors.forename: H
authors.initials: H
authors.lastname: Dufour
authors.forename: M D
authors.initials: MD
authors.lastname: Culler
authors.forename: J P
authors.initials: JP
authors.lastname: Moreau
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
mesh_terms: D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015175:Prolactinoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000634:Aminoquinolines; C111784:BIM 23197; C121506:BIM 23268; D018491:Dopamine Agonists; D006728:Hormones; D009842:Oligopeptides; D010879:Piperazines; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; C046650:quinagolide; D011388:Prolactin; D015282:Octreotide