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

Abstract

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-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 alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta 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.

• Authors: W W Woodmansee, D F Gordon, J M Dowding, B Stolz, R V Lloyd, R A James, W M Wood, E C Ridgway
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 10 Issue 7 Pg. 533-41 (Jul 2000) ISSN: 1050-7256 [Print] United States
• PMID: 10958305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Messenger
• Receptors, Somatostatin
• somatostatin receptor 5
• Thyrotropin
• Thyroxine
• Octreotide

Topics

• Animals
• Gene Expression
• Mice
• Octreotide (metabolism, pharmacology)
• Pituitary Gland (chemistry, drug effects)
• Pituitary Neoplasms (metabolism, pathology)
• RNA, Messenger (analysis)
• Receptors, Somatostatin (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Thyrotropin (analysis, biosynthesis, genetics)
• Thyroxine (blood, pharmacology)
• Tumor Cells, Cultured