Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.
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 alpha 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 Galphaq/Galpha11-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.
Kero
Jukka
J
Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.
Ahmed
Kashan
K
Wettschureck
Nina
N
Tunaru
Sorin
S
Wintermantel
Tim
T
Greiner
Erich
E
Schütz
Günther
G
Offermanns
Stefan
S
D000818:Animals; D002478:Cells, Cultured; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D006042:Goiter / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology*; D013972:Thyrotropin / Q000097:blood
D013972:Thyrotropin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11
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