IGF‐1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH‐stimulated goiter

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.—Ock, S., Ahn, J., Lee, S. H., Kang, H., Offermanns, S., Ahn, H. Y., Jo, Y.S., Shong, M., Cho, B. Y., Jo, D., Abel, E. D., Lee, T. J., Park, W. J., Lee, I.‐K., Kim, J. IGF‐1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH‐stimulated goiter. FASEB J. 27, 4899–4908 (2013). www.fasebj.org