TISSUE-SPECIFIC AND SUBUNIT-SPECIFIC REGULATION OF G-PROTEIN EXPRESSION BY HYPOTHYROIDISM AND HYPERTHYROIDISM

Thyroid hormone status has profound effects on signal transduction in various tissues throughout the body. Therefore, we quantified the signal transducing G-proteins in the rat heart, cerebral cortex, vas deferens and liver by immunoblotting and pertussis toxin labeling in response to chemically induced hypothyroidism (treatment with propylthiouracil) and hyperthyroidism (treatment with triiodothyronine). Levels of the pertussis toxin (PTX) substrates G(ialpha) and G(oalpha) in the heart and vas deferens were inversely correlated with thyroid hormone levels, i.e. G(ialpha) and G(oalpha) were decreased or unchanged in hyperthyroid rats and increased in hypothyroid rats compared to control animals. The cerebral cortex and liver expression of PTX substrates G(ialpha) and G(oalpha) was not affected by changes in thyroid hormone. Regulation of G(salpha) protein was more complex in that G(salpha) was elevated in the hearts from both hypothyroid and hyperthyroid rats compared to control rats, while G(salpha) was unaffected in the other tissues tested. Expression of G-protein beta-subunits was not affected by thyroid status in the heart, liver, or cerebral cortex. Our results suggest that tissue- and G-protein-specific factors are involved in the regulation of G-protein subunits by thyroid hormone. Moreover, cardiac expression of G(salpha) is upregulated by increases or decreases in the normal level of thyroid hormone.