Altered G Protein Expression in Thyroid Adenomas from Hyperthyroid Cats

Ward C.R.

Conference Proceedings, (1998). American College of Veterinary Internal Medicine:

 

Hyperthyroidism is a common endocrinopathy in geriatric cats that resembles toxic nodular goiter in humans. It results from single or multiple hyperplastic thyroid nodules that retain the ability to secrete functional thyroid hormone. Thyroid cell growth and function are normally controlled by TSH/TSH receptor interaction, heterotrimeric G proteins, and cyclic nucleotide metabolism. Investigations into the pathogenesis of human toxic nodular goiter have demonstrated alterations of G protein expression or activation that appear to be responsible for the clinical disease. The purpose of this study was to investigate whether similar changes in G protein expression may be involved in the pathogenesis of feline hyperthyroidism. Adenomatous thyroids were surgically excised from client-owned hyperthyroid cats. The diagnosis of hyperthyroidism was based upon the presence of appropriate clinical signs, elevated serum T4 concentrations, and histology of excised tissue. Normal thyroids were removed from healthy cats euthanized in other experimental studies. Serum T4 concentrations and thyroid histology were normal in the control animals. Thyroid tissue was frozen in liquid nitrogen, and enriched membrane preparations were made. The expression of G, and G classes of heterotrimeric G proteins was determined at the protein level by western blot analysis using specific anti-peptide antibodies. Relative protein amounts were quantified using densitometry and each was compared to its own control. Adenomatous thyroid tissue showed a significant 64%(± 17, p<O.Ol) decrease in G,« levels over control tissue. These experiments were repeated on tissues from 4 different hyperthyroid and euthyroid animals. We conclude that the altered expression of Ga may be involved in the pathogenesis of feline hyperthyroidism.