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

Lookup NU author(s): Dr Robert James


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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(R) on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), 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-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR(R) alone had no effect on any parameter measured. However, Sandostatin LAR(R) combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR(R) 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.

Publication metadata

Author(s): James RA; Woodmansee WW; Gordon DF; Dowding JM; Stolz B; Lloyd RV; Wood WM; Ridgway EC

Publication type: Article

Publication status: Published

Journal: Thyroid

Year: 2000

Volume: 10

Issue: 7

Pages: 533-541

ISSN (print): 1050-7256

ISSN (electronic): 1557-9077

Publisher: Mary Ann Liebert, Inc. Publishers


DOI: 10.1089/thy.2000.10.533


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