Somatostatin receptor subtypes 2 and 5 differentially affect proliferationin vitro of the human medullary thyroid carcinoma cell line TT

Somatostatin and its receptors (SSTR1 to SSTR5) are expressed in normal hum an parafollicular C cells and medullary thyroid carcinoma (MTC), but the ro le of SSTR subtypes in cell growth regulation is still not clear. The prese nt study demonstrates that the human MTC cell line TT stably expresses all the SSTR subtypes and responds to SSTR2 and SSTR5 activation by subtype-sel ective agonists with two different patterns in terms of [H-3]thymidine ([H- 3]thy! incorporation and cell number. The SSTR2 preferential agonists (BIM- 23120, BIM-23197, BIM-23190, and BIM-23014; 10(-9)-10(-6) M), significantly suppressed [H-3]thy incorporation (58-13%) and reduced cell proliferation (50-28%), whereas the SSTR5-selective agonist, BIM-23206 (10(-9)-10(-6) M), significantly increased [H-3]thy incorporation in TT cells (80-175%), but failed to influence cell proliferation. SSTR2 antagonist (BIM-23627) counte racted the action of SSTR2 preferential agonists on TT cells. Furthermore, increasing concentrations of SSTR5-selective agonists, BIM-23206, dose-depe ndently prevented the suppression of TT cell [H-3]thy incorporation and pro liferation produced by SSTR2 preferential agonist, BIM-23120, showing an an tagonism between these compounds. The following conclusions were reached: 1 ) the human MTC cell line TT expresses all SSTR subtypes; 2) SSTR2 activati on inhibits DNA synthesis and cell proliferation, whereas SSTR5 activation increases DNA synthesis; and 3) SSTR2 preferential agonist (BIM-23120) can antagonise SSTR5-selective agonist (BIM-23206) action and vice versa. These findings suggest a tissue-specific function and a tissue-specific interact ion between the two receptors.