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  • Author or Editor: Cynthia R. Ward x
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Abstract

Objective—To evaluate alterations in ligand-stimulated activity of G proteins in thyroid gland cells of hyperthyroid cats.

Sample Population—Membranes of thyroid gland cells isolated from 5 hyperthyroid cats and 3 age-matched euthyroid (control) cats immediately after the cats were euthanatized.

Procedures—Isolated thyroid cell membranes were treated with thyroid-stimulating hormone (TSH), and activation of G protein was quantified by measurement of the binding of guanosine triphosphate γ labeled with sulfur 35 (GTPγ35S). The separate effects of G-protein inhibitory (Gi) and G-protein stimulatory (Gs) proteins were determined by the use of pertussis toxin and cholera toxin, respectively.

Results—Thyroid cell membranes from hyperthyroid cats had higher basal GTPγ35S binding than did thyroid cell membranes from euthyroid cats. Thyroid cell membranes from hyperthyroid and euthyroid cats had a concentration-dependent increase in TSH-stimulated GTPγ35S binding over the TSH range of 0 to 100 mU/mL, with maximal activity at 1 to 100 mU/mL for both. The percentage increase in GTPγ35S binding stimulated by TSH was similar in magnitude between the membranes from hyperthyroid and euthyroid cats. The TSH-stimulated activation of Gs and Gi was not different between euthyroid and hyperthyroid cats.

Conclusions and Clinical Relevance—Ligand-stimulated activation of G proteins was the same in thyroid cell membranes obtained from hyperthyroid and euthyroid cats. Therefore, alterations in inherent Gs or Gi activities did not appear to be part of the pathogenesis of hyperthyroidism in cats.

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in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of dexamethasone or synthetic ACTH administration on endogenous ACTH concentrations in healthy dogs.

Animals—10 healthy neutered dogs.

Procedures—Each dog received dexamethasone (0.01 mg/kg), synthetic ACTH (5 μg/kg), or saline (0.9% NaCl) solution (0.5 mL) IV at intervals of ≥ 30 days. Plasma endogenous ACTH concentrations were measured before (baseline; time 0) and 1, 8, 12, and 24 hours after drug administration; serum cortisol concentrations were measured before and 1 hour after synthetic ACTH and saline solution administration and 8 hours after dexamethasone administration.

Results—Analysis of serum cortisol concentrations confirmed effects of drug administration. Dexamethasone significantly decreased the endogenous ACTH concentration from the baseline value at both 8 and 12 hours. Synthetic ACTH administration significantly decreased the endogenous ACTH concentration from the baseline value at 8 hours. Saline solution administration had no significant effect on endogenous ACTH concentration.

Conclusions and Clinical Relevance—Dexamethasone and synthetic ACTH administered IV at doses used routinely during testing for hyperadrenocorticism caused significant but transient reductions of endogenous ACTH concentrations in healthy dogs. Thus, a 2-hour washout period following ACTH stimulation testing before collection of samples for measurement of the endogenous ACTH concentration may be insufficient. Although this effect has not been verified in dogs with hyperadrenocorticism, these data suggested that samples for measurement of endogenous ACTH concentrations should be obtained before or > 8 hours after initiation of an ACTH stimulation test or before or > 12 hours after the start of a low-dose dexamethasone suppression test.

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in American Journal of Veterinary Research

Abstract

Objective—To determine whether expression of G proteins (Gi and Gs) is altered in thyroid gland adenomas obtained from hyperthyroid cats.

Sample Population—Adenomatous thyroid glands obtained from 8 hyperthyroid cats and thyroid glands obtained from 4 age-matched euthyroid cats.

Procedure—Expression of Gi and Gs was quantified in enriched membrane preparations of thyroid gland tissue, using immunoblotting with Gi and Gs antibodies and toxin-catalyzed ADP-ribosylation.

Results—Expression of Gi was significantly reduced in thyroid gland adenomas from hyperthyroid cats, compared with normal thyroid gland tissue from euthyroid cats. Expression of Gs was similar between the 2 groups.

Conclusions and Clinical Relevance—A decrease in expression of Gi in adenomatous thyroid glands of cats may reduce the negative inhibition of the cAMP cascade in thyroid cells, leading to autonomous growth and hypersecretion of thyroxine. Understanding the molecular mechanisms for hyperthyroidism in cats may lead to better treatment or, ultimately, prevention of the disease. (Am J Vet Res 2000;61:874–879)

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in American Journal of Veterinary Research

Abstract

Objective—To identify within guanosine triphosphate–binding proteins (G proteins) the subset of inhibitory G proteins (Gi) that have decreased expression in adenomatous thyroid glands obtained from hyperthyroid cats.

Sample Population—Adenomatous thyroid glands obtained from 5 hyperthyroid cats and normal thyroid glands obtained from 3 age-matched euthyroid cats.

Procedure—Expression of Gi1, Gi2, and Gi3 in enriched membrane preparations from thyroid glands was quantified by use of immunoblotting with Gi subtype-specific antibodies.

Results—Expression of Gi2 was significantly decreased in tissues of hyperthyroid glands, compared with expression in normal thyroid tissue. Expression of Gi1 and Gi3 was not significantly different between normal thyroid tissues and tissues from hyperthyroid glands.

Conclusions and Clinical Relevance—A decrease in Gi2 expression decreases inhibition of adenylyl cyclase and allows a relative increase in stimulatory G protein expression. This results in increased amounts of cAMP and subsequent unregulated mitogenesis and hormone production in hyperthyroid cells. Decreased Gi2 expression may explain excessive growth and function of the thyroid gland in cats with hyperthyroidism. (Am J Vet Res 2005;66:1478–1482)

Full access
in American Journal of Veterinary Research