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
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.