Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro.
OBJECTIVE
Somatostatin is a powerful inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogs in humans causes a reduction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas. Less studied are the effects of somatostatin agonists on non-functioning pituitary adenomas (NFPAs). In this study we characterized the effects of somatostatin and its analog lanreotide on the proliferation of NFPAs in vitro and the intracellular mechanisms involved.


METHODS
Twenty-three NFPA post-surgical specimens were analyzed for somatostatin receptor (SSTR) expression and 12 of them were cultured in vitro to study somatostatin's effects on cell proliferation, assessed by means of [(3)H]thymidine uptake, and the intracellular signaling.


RESULTS
One or more SSTR subtypes were expressed in 90% of the adenomas tested. Somatostatin and lanreotide treatment inhibited phorbol myristate acetate (PMA)-induced cell proliferation. Vanadate pretreatment reversed somatostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect. In the only adenoma tested, somatostatin directly induced a tyrosine phosphatase activity. Somatostatin and lanreotide caused also a significant inhibition of voltage-sensitive calcium channel activity induced by 40mmol/l K(+) depolarization in microfluorimetric analysis.


CONCLUSIONS
These data show that somatostatin and lanreotide inhibit human NFPA cell proliferation in vitro, and suggest that activation of tyrosine phosphatases and inhibition of the activity of voltage-dependent calcium channels may represent intracellular signals mediating this effect.
Florio
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Service of Pharmacology and Neuroscience, National Institute for Cancer Research (IST), Neuroscience Unit, Advanced Biotechnology Center (CBA), Largo Rosanna Benzi 10, 16132 Genoa, Italy.
Thellung
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Arena
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Corsaro
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Spaziante
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Gussoni
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Acuto
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Giusti
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Giordano
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Schettini
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D000236:Adenoma / Q000188:drug therapy* / Q000473:pathology; D015220:Calcium Channels / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin