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.