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 inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT₄]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR®, on thyrotropic tumor growth, thyrotropin growth factor-β (TSH-β), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT₄ replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-β mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR® alone had no effect on any parameter measured. However, Sandostatin LARρ combined with LT₄ synergistically inhibited TSH-β mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR® required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.