Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter

Abstract

The production and growth regulatory activity of transforming growth factor β were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor β was produced in normal and in diseased thyroid glands. Transforming growth factor β mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor β mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor β protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 μM) to the culture medium. Recombinant transforming growth factor β did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growht factor, transforming growth factor α, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor β may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor β production and decreased responsiveness to transforming growth factor β may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.