Somatostatin analogs in vitro effects in a growth hormone-releasing hormone-secreting bronchial carcinoid.
A 29-yr-old woman presented with acromegaly, pituitary gland enlargement, and an isolated pulmonary mass of 3.3 cm in diameter, which displayed a very high tracer uptake after OctreoScan. Plasma GHRH levels were markedly elevated. The patient underwent left lung upper lobectomy, and histopathology disclosed a bronchial atypical carcinoid. The tissue was examined for somatostatin (SRIH) receptor subtypes (SSTRs) 1-5 expression by RT-PCR. Cultured tumor cells were treated with SRIH, lanreotide (BIM-23014), or SRIH analogs selective for SSTR2 (BIM-23120), SSTR5 (BIM-23206), or SSTR1 (BIM-23926). GHRH was measured in the medium after 6 h, and cell viability was assessed after 48 h. RT-PCR analysis showed expression of SSTR1, -2, and -5. GHRH secretion was significantly reduced by SRIH (-50%), Lan (-35%), as well as by the SSTR2, SSTR5, and SSTR1 selective agonists (-55, -75, and -20%, respectively), whereas cell viability was not affected. Our data show SSTR expression in a GHRH-secreting bronchial carcinoid and provide evidence that, in vitro, selective SSTR activation differently inhibit ectopic GHRH secretion. These findings suggest that SSTR-specific SRIH analogs may be useful in the medical therapy of GHRH-secreting bronchial carcinoids.
Zatelli
Maria Chiara
MC
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
Maffei
Pietro
P
Piccin
Daniela
D
Martini
Chiara
C
Rea
Federico
F
Rubello
Domenico
D
Margutti
Angelo
A
Culler
Michael D
MD
Sicolo
Nicola
N
degli Uberti
Ettore C
EC
D000328:Adult; D001984:Bronchial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000145:classification
D017481:Receptors, Somatostatin; D013007:Growth Hormone-Releasing Hormone