title: TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia.
abstract: Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r(+/-), and Igf1r(-/-) genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r(+/-) and Igf1r(-/-) mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis.
authors: Department of Internal Medicine, University of Leipzig, Germany.
authors: Kathrin
authors: K
authors: Müller
authors: Dagmar
authors: D
authors: Führer
authors: Jens
authors: J
authors: Mittag
authors: Nora
authors: N
authors: Klöting
authors: Matthias
authors: M
authors: Blüher
authors: Roy E
authors: RE
authors: Weiss
authors: Marie-Christine
authors: MC
authors: Many
authors: Kurt Werner
authors: KW
authors: Schmid
authors: Knut
authors: K
authors: Krohn
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D050033:Thyroid Dysgenesis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*
chemical_list: D013972:Thyrotropin; D000242:Cyclic AMP; D017526:Receptor, IGF Type 1