Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro

Citation
T. Florio et al., Somatostatin and its analog lanreotide inhibit the proliferation of dispersed human non-functioning pituitary adenoma cells in vitro, EUR J ENDOC, 141(4), 1999, pp. 396-408
Citations number
51
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
EUROPEAN JOURNAL OF ENDOCRINOLOGY
ISSN journal
08044643 → ACNP
Volume
141
Issue
4
Year of publication
1999
Pages
396 - 408
Database
ISI
SICI code
0804-4643(199910)141:4<396:SAIALI>2.0.ZU;2-U
Abstract
Objective: Somatostatin is a powerful inhibitor of hormone secretion and ce ll proliferation. Treatment with somatostatin analogs in humans causes a re duction in size and secretory activity of some endocrine tumors, including somatotropic pituitary adenomas, Less studied are the effects of somatostat in 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. Design: Twenty-three NFPA post-surgical specimens were analyzed for somatos tatin receptor (SSTR) expression and 12 of them were cultured in vitro to s tudy somatostatin's effects on cell proliferation assessed by means of [H-3 ]thymidine uptake. and the intracellular signaling, Results: One or more SSTR subtypes were expressed in 90% of the adenomas te sted. Somatostatin and lanreotide treatment inhibited phorbol myristate ace tate (PMA)-induced cell proliferation, Vanadate pretreatment reversed somat ostatin and lanreotide inhibition of PMA-induced DNA synthesis suggesting a n involvement of tyrosine phosphatase in this effect. In the only adenoma t ested, somatostatin directly induced a tyrosine phosphatase activity, Somat ostatin and lanreotide caused also a significant inhibition of voltage-sens itive calcium channel activity induced by 40 mmol/l K+ depolarization in mi crofluorimetric 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 ch annels may represent intracellular signals mediating this effect.