ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2007) 14 OC3.1 
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Multiple somatostatin receptor subtypes activation reduces cell viability in non-functioning pituitary adenomas by inhibiting Vascular Endothelial Growth Factor secretion

Maria Chiara Zatelli1, Daniela Piccin1, Federico Tagliati1, Maria Rosaria Ambrosio1, Antonio Bianchi2, Marta Bondanelli1, Herbert A Schmid3, Massimo Scanarini4, Laura De Marinis2, Giulio Maira5 & Ettore C degli Uberti1

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Somatostatin (SRIF) analogs have been employed in medical therapy of non-functioning pituitary adenomas (NFA), with contrasting results. Previous evidence showed that SRIF can exert its antiproliferative effects by reducing Vascular Endothelial Growth Factor (VEGF) secretion and action, and that VEGF expression may be related to pituitary tumor growth. The aim of our study was to clarify the possible effects of a multireceptor SRIF ligand on VEGF secretion and cell proliferation in human NFA primary cultures, we assessed SRIF receptors (SSTR1-5) expression and the in vitro effects on VEGF secretion and on cell viability of SRIF and of the stable SRIF analogue pasireotide (SOM230) which activates SSTR1, 2, 3 and 5. Twenty-five NFA were examined by RT-PCR for expression of α-subunit, SSTR, VEGF, and VEGF receptors 1 (VEGF-R1) and 2 (VEGF-R2). Primary cultures were tested with SRIF and with pasidreotide. All NFA samples expressed α-sub, VEGF and VEGFR-1 and 2, while SSTR expression pattern was highly variable. Two different groups were identified according to VEGF secretion inhibition by SRIF. VEGF secretion and cell viability were reduced by SRIF and pasireotide in the “responder” group, but not in the “non responder” group, including NFA expressing SSTR5. SRIF and pasireotide completely blocked Forskolin-induced VEGF secretion. In addition, SRIF and pasireotide completely abrogated the promoting effects of VEGF on NFA cell viability. Our data demonstrate that pasireotide can inhibit NFA cell viability by inhibiting VEGF secretion, and suggest that the multireceptor-SSTR agonist pasireotide might be useful in medical therapy of selected NFA.

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