Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development
Jukka Kero, … , Günther Schütz, Stefan Offermanns
Jukka Kero, … , Günther Schütz, Stefan Offermanns
Published September 4, 2007
Citation Information: J Clin Invest. 2007;117(9):2399-2407. https://doi.org/10.1172/JCI30380.
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Research Article Endocrinology

Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development

Abstract

The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein–coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase–dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the α subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Gαq/Gα11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

Authors

Jukka Kero, Kashan Ahmed, Nina Wettschureck, Sorin Tunaru, Tim Wintermantel, Erich Greiner, Günther Schütz, Stefan Offermanns

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Figure 2

Physiological consequences of the thyrocyte-specific Gαq/Gα11 deficiency.

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Physiological consequences of the thyrocyte-specific Gαq/Gα11 deficiency...
Serum TSH (A) and T4 levels (B) in wild-type and Tc-Gαq/Gα11–KO animals at the indicated ages. ***P < 0.001. (C) Western blot of thyroid gland lysates from wild-type and Tc-Gαq/Gα11–KO mice with normal (<150 ng/ml) and elevated (>500 ng/ml) TSH levels probed with antibodies recognizing Gαq/Gα11, Gαs or tubulin. (D) Effect of increasing concentrations of TSH on cAMP formation in thyrocytes prepared from wild-type or Tc-Gαq/Gα11–KO mice with normal or high TSH levels. Values are mean ± SEM.