Quantitative and functional expression of somatostatin receptor subtypes in human prolactinomas

Recently, it was demonstrated that somatostatin analogs preferential for th e SSTR5 subtype suppress PRL release hom prolactinoma cell cultures by 30-4 0%. These data supported the idea of somatostatin receptor subtype-specific control of PRL secretion in such tumors. The present study examines the qu antitative profile of SSTRs messenger ribonucleic acid (mRNA) in 10 PRL-sec reting tumors and correlates the expression with the ability of native soma tostatins (SS14 and SS28), SSTR2 preferential analogs (octreotide and BIM-2 3197), and the SSTR5 preferential analog BIM-23268 to suppress PRL secretio n. 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 e xpressed in prolactinomas (1296 +/- 669 pg/pg GAPDH). SSTR5 mRNA expression correlated with PRL inhibition induced by both SRIF14 and SRIF28. Among th e different analogs tested, only BIM-23268 produced inhibition of PRL relea se similar to that achieved with the native peptides. Its EC,, for PRL supp ression was 0.28 +/- 0.10 nmol/L. No additive effects on PRL suppression we re achieved by cotreatment of the tumor cells with SSTR2 and SSTR5 preferen tial analogs. In the same tumor cell cultures, quinagolide, a potent dopami ne agonist, produced a dose-dependent inhibition of PRL with an EC50 at lea st 10 times lower than that of BIM-23268. Coincubation of quinagolide and B IM-23268, particularly in tumor cells resistant to dopamine agonist treatme nt, did not produce additive effects on PRL suppression. Tn conclusion, pro lactinomas have a specific pattern of SSTR subtype mRNA expression (SSTR5 a nd SSTR1). SSTR5 expression is correlated to PRL regulation. These inhibito ry effects are superimposable, at a higher concentration, to those of the d opamine agonists, but are not additive, particularly in the adenomas resist ant to dopaminergic suppression of PRL release.