Zatelli M C, Tagliati F, Taylor J E, Rossi R, Culler M D, degli Uberti E C
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, 44100 Ferrara, Italy.
J Clin Endocrinol Metab. 2001 May;86(5):2161-9. doi: 10.1210/jcem.86.5.7489.
Somatostatin and its receptors (SSTR1 to SSTR5) are expressed in normal human parafollicular C cells and medullary thyroid carcinoma (MTC), but the role of SSTR subtypes in cell growth regulation is still not clear. The present study demonstrates that the human MTC cell line TT stably expresses all the SSTR subtypes and responds to SSTR2 and SSTR5 activation by subtype-selective agonists with two different patterns in terms of [(3)H]thymidine ([(3)H]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 [(3)H]thy incorporation (58-13%) and reduced cell proliferation (50-28%), whereas the SSTR5-selective agonist, BIM-23206 (10(-9)-10(-6) M), significantly increased [(3)H]thy incorporation in TT cells (80-175%), but failed to influence cell proliferation. SSTR2 antagonist (BIM-23627) counteracted the action of SSTR2 preferential agonists on TT cells. Furthermore, increasing concentrations of SSTR5-selective agonists, BIM-23206, dose-dependently prevented the suppression of TT cell [(3)H]thy incorporation and proliferation produced by SSTR2 preferential agonist, BIM-23120, showing an antagonism between these compounds. The following conclusions were reached: 1) the human MTC cell line TT expresses all SSTR subtypes; 2) SSTR2 activation 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 interaction between the two receptors.
生长抑素及其受体（SSTR1至SSTR5）在正常人类甲状腺滤泡旁C细胞和甲状腺髓样癌（MTC）中表达，但SSTR亚型在细胞生长调节中的作用仍不清楚。本研究表明，人MTC细胞系TT稳定表达所有SSTR亚型，并通过亚型选择性激动剂对SSTR2和SSTR5激活产生反应，在[³H]胸苷（[³H]thy）掺入和细胞数量方面呈现两种不同模式。SSTR2优先激动剂（BIM - 23120、BIM - 23197、BIM - 23190和BIM - 23014；10⁻⁹ - 10⁻⁶ M）显著抑制[³H]thy掺入（58 - 13%）并减少细胞增殖（50 - 28%），而SSTR5选择性激动剂BIM - 23206（10⁻⁹ - 10⁻⁶ M）显著增加TT细胞中的[³H]thy掺入（80 - 175%），但未能影响细胞增殖。SSTR2拮抗剂（BIM - 23627）抵消了SSTR2优先激动剂对TT细胞的作用。此外，SSTR5选择性激动剂BIM - 23206浓度增加时，剂量依赖性地阻止了SSTR2优先激动剂BIM - 23120对TT细胞[³H]thy掺入和增殖的抑制，显示出这些化合物之间的拮抗作用。得出以下结论：1）人MTC细胞系TT表达所有SSTR亚型；2）SSTR2激活抑制DNA合成和细胞增殖，而SSTR5激活增加DNA合成；3）SSTR2优先激动剂（BIM - 23120）可拮抗SSTR5选择性激动剂（BIM - 23206）的作用，反之亦然。这些发现提示了两种受体之间的组织特异性功能和组织特异性相互作用。
