Somatostatin receptor subtype 1 selective activation in human growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas: Effects on cell viability, GH, and PRL secretion

Somatostatin ( SRIF) analogs interacting with SRIF receptor subtype ( SSTR) 2 and SSTR5 are known to reduce secretion in GH- secreting pituitary adenomas. We investigated the effects of SRIF and a SSTR1 selective agonist, BIM-23926, on GH and prolactin ( PRL) secretion and cell viability in primary cultures deriving from 15 GH- and PRL- secreting adenomas expressing SSTR1. Quantitative RT- PCR showed SSTR1 mRNA mean levels of 6 +/- 2.2 x 10(4) molecules/mug reverse- transcribed total RNA. SSTR2 and SSTR5 were frequently expressed ( 93.3%), on the contrary of SSTR3 ( 53.3%) and SSTR4 ( 6.7%). GH secretion was significantly reduced by SRIF and BIM23926 ( 45 +/- 8.6% and 32 +/- 18.1% inhibition, respectively) as well as PRL secretion ( 16.1 +/- 4% and 19.7 +/- 3.5% inhibition, respectively). After treatment with SRIF and BIM- 23926, cell viability was significantly reduced by 17.5 +/- 5% and 20 +/- 3.9%, respectively. SSTR1 mRNA levels correlated with the degree of GH and PRL secretion inhibition. These results demonstrate that SSTR1 selective activation inhibits hormone secretion and cell viability in GH- and PRL- secreting adenomas in vitro and suggest that SRIF analogs with affinity for SSTR1 may be useful to control hormone hypersecretion and reduce neoplastic growth of pituitary adenomas.