title: 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 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.
authors.affiliation: Department of Medicine, University of Colorado Health Science Center, Denver 80262, USA. Andy.James@btinternet.corn
authors.forename: R A
authors.initials: RA
authors.lastname: James
authors.forename: V D
authors.initials: VD
authors.lastname: Sarapura
authors.forename: C
authors.initials: C
authors.lastname: Bruns
authors.forename: F
authors.initials: F
authors.lastname: Raulf
authors.forename: J M
authors.initials: JM
authors.lastname: Dowding
authors.forename: D F
authors.initials: DF
authors.lastname: Gordon
authors.forename: W M
authors.initials: WM
authors.lastname: Wood
authors.forename: E C
authors.initials: EC
authors.lastname: Ridgway
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013972:Thyrotropin; D012194:RNA-Directed DNA Polymerase; D013974:Thyroxine