Somatostatin analogs and chimeric somatostatin-dopamine molecules differentially regulate human growth hormone and prolactin gene expression and secretion in vitro.
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.
Division of Endocrinology, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048, USA. anna.gruszka@umed.lodz.pl
Anna
A
Gruszka
Michael D
MD
Culler
Shlomo
S
Melmed
D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
C519495:BIM 23120; C519496:BIM 23206; C577073:BIM-23A761; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D013004:Somatostatin; D011388:Prolactin; C531242:TBR-760; D004298:Dopamine