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-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.
Woodmansee
W W
WW
Division of Endocrinology, University of Colorado Health Sciences Center, Denver 80262, USA. Whitney.Woodmansee@UCHSC.edu
Gordon
D F
DF
Dowding
J M
JM
Stolz
B
B
Lloyd
R V
RV
James
R A
RA
Wood
W M
WM
Ridgway
E C
EC
D000818:Animals; D015870:Gene Expression; D051379:Mice; D015282:Octreotide / Q000378:metabolism / Q000494:pharmacology*; D010902:Pituitary Gland / Q000737:chemistry / Q000187:drug effects; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013972:Thyrotropin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; D013972:Thyrotropin; D013974:Thyroxine; D015282:Octreotide