Thyroid hormone-induced expression of specific somatostatin receptor subtypes correlates with involution of the TtT-97 murine thyrotrope tumor.
Following the protracted hypothyroid state, treatment with thyroid hormone will induce a decline in TSH and reduce thyrotrope hyperplasia. Somatostatin is a hypothalamic peptide that has been implicated in the negative regulation of TSH secretion in the thyrotrope. Moreover, analogs of native somatostatin have potent TSH-reducing and growth-retarding effects on human thyrotropinomas. The TtT-97 tumor is an in vivo murine thyrotropic model that has retained its physiological response to thyroid hormone. This study investigates the regulation of somatostatin receptor subtypes in this tumor. TtT-97 tumors, actively growing in hypothyroid mice, did not express any significant somatostatin receptor messenger RNA (mRNA) or protein. T4 administration resulted in a reduction in TSH beta mRNA expression and a marked degree of tumor involution. Analysis of residual tumors from thyroid hormone-treated mice showed the specific up-regulation of SSTR1 and SSTR5 mRNA subtypes and the appearance of abundant, high affinity SSTR receptor-binding sites within the tumor. Thus, the TtT-97 tumor provides a thyrotrope-specific model in which to study the regulation of somatostatin receptor subtypes by thyroid hormone and correlate this expression with both antisecretory and antiproliferative effects.
James
R A
RA
Department of Medicine, University of Colorado Health Science Center, Denver 80262, USA. Andy.James@btinternet.corn
Sarapura
V D
VD
Bruns
C
C
Raulf
F
F
Dowding
J M
JM
Gordon
D F
DF
Wood
W M
WM
Ridgway
E C
EC
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D015870:Gene Expression / Q000187:drug effects*; D007037:Hypothyroidism / Q000378:metabolism; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*; D013974:Thyroxine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013972:Thyrotropin; D012194:RNA-Directed DNA Polymerase; D013974:Thyroxine