The Inhibitory G Protein, Gi2, Shows Decreased Expression in Adenomatous Thyroid Tissue from Hyperthyroid Cats

Ward C.E., Achenbach S.E. and Peterson M.E.

Conference Proceedings, (2001). American College of Veterinary Internal Medicine:


Feline hyperthyroidism is a common endocrinopathy in cats that resembles toxic nodular goiter (TNG) in humans.  Abnormalities of the TSH receptor-G protein-mediated signal transduction cascade have been shown to be involved in the pathogenesis of human TNG.  Previous work from our laboratory has implicated similar pathogenic mechanisms involved in feline hyperthyroidism.  We demonstrated that adenomatous thyroid tissue from hyperthyroid cats showed significantly decreased expression of inhibitory G proteins (Gi).  Three subtypes of Gi proteins (Gi1, Gi2, Gi3) exist, many with unique signaling activities in certain cell types.  The purpose of this study was to identify which Gi protein subtype(s) showed decreased expression in adenomatous thyroid tissue from hyperthyroid cats. 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 thyroxine concentrations, and histology of excised tissue.  Normal thyroids were removed from aged-matched healthy cats euthanized in other experimental studies.  Serum thyroxine and histology were normal in the control cats. Thyroid tissue was snap frozen in liquid nitrogen, and enriched membrane preparations were made.  The expression of Gi, Gi1, Gi2, and Gi3 were determined at the protein level in normal and hyperthyroid tissue by western blot analysis using specific anti-peptide antibodies.  Relative protein amounts were quantified using densitometry and each was compared to its own control on the same blot.  As seen previously, adenomatous thyroid tissue showed a significant decrease of 53% (P <0.001; n=3) in expression as compared to normal thyroid tissue.  Correspondingly, Gi2 showed significant decrease of 39% (P<0.01; n=3) in adenomatous thyroid tissue as compared to control.  In contrast, Gi1 and Gi3 showed no significant difference in expression from controls (-1.8% and -2.4 %, respectively; P >0.05; n=3).  We conclude that Gi2 is the Gi that shows altered expression in adenomatous tissue and is involved in the pathogenesis of feline hyperthyroid disease.