Tsuzaki S, Moses A C
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215.
Endocrinology. 1990 Jun;126(6):3131-8. doi: 10.1210/endo-126-6-3131.
Somatostatin, a cyclic tetradecapeptide, is both a hypothalamic hormone and a paracrine peptide, with effects on many tissues. Despite the fact that somatostatin can inhibit various cellular events in a number of cell lines, somatostatin is a constituent of medium defined for optimal growth of FRTL5, a line of differentiated and nontransformed rat thyroid follicular cells. In the present study we have evaluated the role of somatostatin in the control of DNA synthesis in FRTL5 cells and have investigated the mechanisms of somatostatin interaction with pathways stimulated by TSH and insulin-like growth factor-I (IGF-I). Somatostatin inhibits TSH-stimulated DNA synthesis and cell proliferation in FRTL5 cells. Maximal effects are observed at somatostatin concentrations of 0.1-10 ng/ml, and the effects are diminished at somatostatin concentrations above 10 ng/ml. Somatostatin also inhibits (Bu)2cAMP-stimulated DNA synthesis, suggesting that the loci of somatostatin action are both proximal and distal to activation of adenylate cyclase. Somatostatin also inhibits DNA synthesis stimulated by insulin-like growth factor-I (IGF-I), a pleiotropic growth factor that works through non-cAMP-dependent pathways. The somatostatin analog octreotide is more potent than native somatostatin in inhibiting DNA synthesis stimulated by either TSH or IGF-I. Somatostatin does not alter TSH or IGF-I binding to FRTL5, demonstrating that somatostatin affects the postreceptor signal transduction pathways stimulated by these factors. We conclude that 1) the use of somatostatin in hormone-supplemented medium for FRTL5 is unnecessary and may inhibit cell growth; 2) somatostatin can inhibit the direct effects of IGF-I on peripheral tissues in addition to its ability to interfere with IGF-I synthesis by inhibiting the synthesis and release of pituitary GH; and 3) somatostatin is a useful tool for dissecting the pathways involved in mediating differentiated function and growth of FRTL5 cells.
生长抑素是一种环状十四肽，既是一种下丘脑激素，也是一种旁分泌肽，对许多组织都有作用。尽管生长抑素能抑制多种细胞系中的各种细胞活动，但它却是为FRTL5（一种分化的、未转化的大鼠甲状腺滤泡细胞系）的最佳生长所定义的培养基的组成成分。在本研究中，我们评估了生长抑素在控制FRTL5细胞DNA合成中的作用，并研究了生长抑素与促甲状腺激素（TSH）和胰岛素样生长因子-I（IGF-I）刺激的信号通路相互作用的机制。生长抑素可抑制FRTL5细胞中TSH刺激的DNA合成和细胞增殖。在生长抑素浓度为0.1 - 10 ng/ml时观察到最大效应，而在生长抑素浓度高于10 ng/ml时效应减弱。生长抑素还能抑制（Bu）2cAMP刺激的DNA合成，这表明生长抑素的作用位点在腺苷酸环化酶激活的近端和远端。生长抑素还能抑制胰岛素样生长因子-I（IGF-I）刺激的DNA合成，IGF-I是一种通过非cAMP依赖途径起作用的多效生长因子。生长抑素类似物奥曲肽在抑制TSH或IGF-I刺激的DNA合成方面比天然生长抑素更有效。生长抑素不会改变TSH或IGF-I与FRTL5的结合，这表明生长抑素影响这些因子刺激的受体后信号转导通路。我们得出以下结论：1）在用于FRTL5的激素补充培养基中使用生长抑素是不必要的，且可能抑制细胞生长；2）生长抑素除了能够通过抑制垂体生长激素（GH）的合成和释放来干扰IGF-I合成外，还能抑制IGF-I对周围组织的直接作用；3）生长抑素是剖析介导FRTL5细胞分化功能和生长的信号通路的有用工具。
