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

Abstract

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.

DESIGN:

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.

• Authors: T Florio, S Thellung, S Arena, A Corsaro, R Spaziante, G Gussoni, G Acuto, M Giusti, G Giordano, G Schettini
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 141 Issue 4 Pg. 396-408 (Oct 1999) ISSN: 0804-4643 [Print] England
• PMID: 10526255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels
• Peptides, Cyclic
• lanreotide
• Somatostatin

Topics

• Adenoma (drug therapy, pathology)
• Calcium Channels (drug effects)
• Cell Division (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Male
• Membrane Potentials (drug effects)
• Middle Aged
• Peptides, Cyclic (pharmacology)
• Pituitary Neoplasms (drug therapy, pathology)
• Somatostatin (analogs & derivatives, pharmacology)
• Tumor Cells, Cultured