Somatostatin analogs and chimeric somatostatin–dopamine molecules differentially regulate human growth hormone and prolactin gene expression and secretion in vitro

Abstract We tested effects of selective somatostatin receptor 2 (SST2) agonist BIM-23120, SST5 agonist BIM-23206 and chimeric somatostatin–dopamine molecules (SRIF/DA) BIM-23A760 and BIM-23A761 on GH and PRL secretion and gene expression in human GH/PRL-secreting pituitary tumors in vitro . In “responders” group BIM-23120 suppressed GH levels by 26 ± 4%, BIM-23206 by 31 ± 5%, BIM-23A760 by 23 ± 4%, BIM-23A761 by 39 ± 8% and D 2 -dopamine agonist BIM-53097 by 31 ± 5%. Using real-time PCR we demonstrated that GH inhibition was not accompanied by decreased GH mRNA levels. PRL secretion was inhibited by BIM-23A760 (29 ± 5%), BIM-23A761 (34 ± 4%), BIM-23206 (26 ± 4%) and BIM-53097 (36 ± 2%). SRIF/DA and BIM-53097 also suppressed PRL mRNA levels. Concluding, SST2 and SST5 agonists and SRIF/DA inhibit GH secretion, but do not suppress GH gene transcription. SRIF/DA and BIM-53097 inhibit both PRL secretion and PRL gene expression. SST5 agonist inhibits PRL secretion, but does not suppress PRL gene expression. D 2 affinity is crucial in SRIF/DA action on PRL gene expression.