title: Somatostatin inhibits deoxyribonucleic acid synthesis induced by both thyrotropin and insulin-like growth factor-I in FRTL5 cells.
abstract: 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.
authors.affiliation: Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215.
authors.forename: S
authors.initials: S
authors.lastname: Tsuzaki
authors.forename: A C
authors.initials: AC
authors.lastname: Moses
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051381:Rats; D013002:Somatomedins / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
chemical_list: D013002:Somatomedins; D013004:Somatostatin; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D004247:DNA; D000242:Cyclic AMP