Evidence for differential effects of selective somatostatin receptor subtype agonists on alpha-subunit and chromogranin a secretion and on cell viability in human nonfunctioning pituitary adenomas in vitro.
Somatostatin (SRIF) analogs interacting with SRIF receptor (SSTR) subtypes SSTR2 and SSTR5 reduce hormone secretion of pituitary adenomas, but their antiproliferative effects are still controversial. We investigated the in vitro effects of SRIF and SSTR-selective agonists interacting with SSTR1 (BIM-23926), SSTR2 (BIM-23120), SSTR5 (BIM-23206), or both SSTR2 and SSTR5 (BIM-23244) on alpha-subunit and chromogranin A secretion and on cell viability of 12 nonfunctioning pituitary adenomas (NFA) expressing SSTR1, SSTR2, and SSTR5, as assessed by RT-PCR. Treatment with SRIF or BIM-23206 did not modify alpha-subunit and chromogranin A secretion, which was significantly inhibited by BIM-23926, BIM-23120, and BIM-23244. SRIF and BIM-23120 did not influence cell viability, which was significantly promoted by BIM-23206 and BIM-23244 and reduced by treatment with BIM-23926. These results demonstrate that, in the selected NFA, the SSTR1-selective agonist inhibits secretory activity and cell viability, the SSTR2-selective agonist inhibits secretion but not cell viability, and the SSTR5-selective agonist does not influence secretion but promotes cell viability. These data can explain the lack of inhibitory effects of currently used SRIF analogs and suggest that drugs acting potently and preferentially on SSTR1 might be useful for medical treatment of NFA.
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
Maria Chiara
MC
Zatelli
Daniela
D
Piccin
Arianna
A
Bottoni
Maria Rosaria
MR
Ambrosio
Angelo
A
Margutti
Roberto
R
Padovani
Massimo
M
Scanarini
John E
JE
Taylor
Michael D
MD
Culler
Luigi
L
Cavazzini
Ettore C
EC
degli Uberti
D000236:Adenoma; D000328:Adult; D000368:Aged; D002470:Cell Survival / Q000187:drug effects; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000819:agonists* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C423390:BIM-23244; C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D013004:Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2