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Thyroid Hormone-Induced Expression of Specific Somatostatin Receptor Subtypes Correlates with Involution of the TtT-97 Murine Thyrotrope Tumor

Abstract 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 nati...

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Published in:Endocrinology (Philadelphia) 1997-02, Vol.138 (2), p.719-724
Main Authors: James, R. Andrew, Sarapura, Virginia D., Bruns, Christian, Raulf, Friedrich, Dowding, Janet M., Gordon, David F., Wood, William M., Ridgway, E. Chester
Format: Article
Language:English
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Summary:Abstract 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 TSHβ 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.
ISSN:0013-7227
1945-7170
DOI:10.1210/endo.138.2.4951