Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development
Jukka Kero, Kashan Ahmed, Nina Wettschureck, Sorin Tunaru, Tim Wintermantel, Erich Greiner, Günther Schütz, Stefan Offermanns
Jukka Kero, Kashan Ahmed, Nina Wettschureck, Sorin Tunaru, Tim Wintermantel, Erich Greiner, Günther Schütz, Stefan Offermanns
View: Text | PDF
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

×

Figure 4

Cellular effects of TSH in wild-type and Tc-Gαq/Gα11–KO mice.

Options: View larger image (or click on image) Download as PowerPoint
Cellular effects of TSH in wild-type and Tc-Gαq/Gα11–KO mice. ...
(A–C) Iodine uptake (A), organification (B), and thyroid hormone release (C) were determined as described in Methods. TSH was administered i.p. at a dose of 100 mIU/100 g body weight. As a control, organification was suppressed by treatment of animals with propylthiouracil (PTU; 0.4 mg/10 g body weight i.p. –24, –12, and 0 h relative to TSH administration). *P < 0.05, ***P < 0.001 versus non–TSH-treated (A and B) or wild-type (C). Results in A–C are representative of experiments performed at least 3 times with 3–4 animals per group. (D) Periodic acid-Schiff–stained colloid droplets in follicle epithelial cells of thyroid from wild-type and Tc-Gαq/Gα11–KO animals treated or not with TSH (100 mIU/10 g body weight) for 5 hours (n = 6). ***P < 0.001 versus wild-type. (E) Representative sections of wild-type and Tc-Gαq/Gα11–KO animals treated for 5 hours with TSH after staining with periodic acid-Schiff stain. Arrows indicate clusters of droplets. Scale bars: 50 μm.