title: IGF-1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH-stimulated goiter.
abstract: Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.
authors: 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University, 224-1 Heuk Seok-dong, Dongjak-ku Seoul 156-755, Korea. jtkim@cau.ac.kr.
authors: Sangmi
authors: S
authors: Ock
authors: Jihyun
authors: J
authors: Ahn
authors: Seok Hong
authors: SH
authors: Lee
authors: Hyun
authors: H
authors: Kang
authors: Stefan
authors: S
authors: Offermanns
authors: Hwa Young
authors: HY
authors: Ahn
authors: Young Suk
authors: YS
authors: Jo
authors: Minho
authors: M
authors: Shong
authors: Bo Youn
authors: BY
authors: Cho
authors: Daewoong
authors: D
authors: Jo
authors: E Dale
authors: ED
authors: Abel
authors: Tae Jin
authors: TJ
authors: Lee
authors: Woo Jin
authors: WJ
authors: Park
authors: In-Kyu
authors: IK
authors: Lee
authors: Jaetaek
authors: J
authors: Kim
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D015536:Down-Regulation; D006042:Goiter / Q000139:chemically induced / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters; D010472:Perchlorates / Q000633:toxicity; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics*; D017670:Sodium Compounds / Q000633:toxicity; D027981:Symporters; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*
chemical_list: D013956:Antithyroid Agents; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D010472:Perchlorates; C484257:Slc16a2 protein, mouse; D017670:Sodium Compounds; D027981:Symporters; D008713:Methimazole; D013972:Thyrotropin; C031068:sodium perchlorate; D017526:Receptor, IGF Type 1; D013974:Thyroxine
keywords: MCT8; T4; hypertrophy; proliferation