G Proteins Recognized as Critical Modulators of Thyroid Function

Researchers working with a line of mice genetically engineered to lack the alpha subunits of the G proteins Gq and G11 have found that these animals had reduced thyroid gland function and in many cases displayed symptoms similar to individuals with hypothyroidism.

G proteins, short for guanine nucleotide binding proteins, are a family of proteins involved in second messenger cascades. Their signaling mechanism uses the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) as a general molecular "switch” function to regulate cell processes. The name G protein usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the large G proteins. These proteins are activated by G protein-coupled receptors and are made up of alpha, beta, and gamma subunits. There are also small G proteins that are monomeric, but also bind GTP and GDP and are involved in signal transduction.

Investigators at the University of Heidelberg (Germany; www.uni-heidelberg.de) genetically engineered a line of mice to lack the alpha subunits in both the Gq and G11 proteins present in the animal's thyroid tissues. They reported in the August 9, 2007, online edition of the Journal of Clinical Investigation that these mice 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 Gq/G11-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.

The authors concluded, "Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.” Drugs to this effect would be of therapeutic benefit for individuals with diseases characterized by increased thyroid gland function and/or growth.


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