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: Sangmi Ock, Jihyun Ahn, Seok Hong Lee, Hyun Kang, Stefan Offermanns, Hwa Young Ahn, Young Suk Jo, Minho Shong, Bo Youn Cho, Daewoong Jo, E Dale Abel, Tae Jin Lee, Woo Jin Park, In-Kyu Lee, Jaetaek Kim
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 27 Issue 12 Pg. 4899-908 (Dec 2013) ISSN: 1530-6860 [Electronic] United States
• PMID: 23982142 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antithyroid Agents
• Membrane Transport Proteins
• Monocarboxylic Acid Transporters
• Perchlorates
• Slc16a2 protein, mouse
• Sodium Compounds
• Symporters
• Methimazole
• Thyrotropin
• sodium perchlorate
• Receptor, IGF Type 1
• Thyroxine

Topics

• Animals
• Antithyroid Agents (pharmacology)
• Down-Regulation
• Goiter (chemically induced, metabolism)
• Membrane Transport Proteins (genetics, metabolism)
• Methimazole (pharmacology)
• Mice
• Mice, Knockout
• Monocarboxylic Acid Transporters
• Perchlorates (toxicity)
• Receptor, IGF Type 1 (deficiency, genetics)
• Sodium Compounds (toxicity)
• Symporters
• Thyroid Gland (drug effects, metabolism, pathology)
• Thyrotropin (metabolism)
• Thyroxine (metabolism)