TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia

Kathrin Müller, Dagmar Führer, Jens Mittag, Nora Klöting, Matthias Blüher, Roy E Weiss, Marie Christine Many, Kurt Werner Schmid, Knut Krohn

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 Igf1rinactivation 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 thesodium-iodide-symporter in bothIgf1r +/- 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.

Original languageEnglish (US)
Pages (from-to)1867-1879
Number of pages13
JournalMolecular Endocrinology
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

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IGF Type 1 Receptor
Hyperplasia
Thyroid Gland
Thyroid Hormones
Messenger RNA
IGF Type 2 Receptor
Symporters
Weights and Measures
Thyrotropin Receptors
Iodide Peroxidase
Insulin Receptor
Iodides
Insulin-Like Growth Factor I
Morphogenesis
Protein-Tyrosine Kinases
Proteins
Homeostasis
Genotype
Body Weight
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia. / Müller, Kathrin; Führer, Dagmar; Mittag, Jens; Klöting, Nora; Blüher, Matthias; Weiss, Roy E; Many, Marie Christine; Schmid, Kurt Werner; Krohn, Knut.

In: Molecular Endocrinology, Vol. 25, No. 11, 01.11.2011, p. 1867-1879.

Research output: Contribution to journalArticle

Müller, K, Führer, D, Mittag, J, Klöting, N, Blüher, M, Weiss, RE, Many, MC, Schmid, KW & Krohn, K 2011, 'TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia', Molecular Endocrinology, vol. 25, no. 11, pp. 1867-1879. https://doi.org/10.1210/me.2011-0065
Müller, Kathrin ; Führer, Dagmar ; Mittag, Jens ; Klöting, Nora ; Blüher, Matthias ; Weiss, Roy E ; Many, Marie Christine ; Schmid, Kurt Werner ; Krohn, Knut. / TSH compensates thyroid-specific IGF-I receptor knockout and causes papillary thyroid hyperplasia. In: Molecular Endocrinology. 2011 ; Vol. 25, No. 11. pp. 1867-1879.
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