The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth . Somatostatin has been implicated as a synergistic factor in the inhibitio n of thyrotrope function. We have previously shown that pharmacological dos es of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin recept or type 5 (sst5) mRNA and somatostatin receptor binding. In the current stu dy, we examined the effect of physiological thyroid hormone replacement alo ne or in combination with the long-acting somatostatin analogue, Sandostati n LAR(R) on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-b eta), and sst5 mRNA expression, as well as somatostatin receptor binding si tes. Physiological LT4 replacement therapy resulted in tumor shrinkage in a ssociation with increased sst5 mRNA levels, reduced TSH-beta mRNA levels an d enhanced somatostatin receptor binding. Sandostatin LAR(R) alone had no e ffect on any parameter measured. However, Sandostatin LAR(R) combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tu mor weights to a greater degree. In this paradigm, Sandostatin LAR(R) requi red a euthyroid status to alter thyrotrope parameters. These data suggest a n important interaction between the somatostatinergic system and thyroid ho rmone in the regulation of thyrotrope cell structure and function.