Human Medullary Thyroid Carcinoma: Control of Calcitonin Secretion In Vivo and in Tissue Culture

Abstract

A patient with medullary carcinoma of the thyroid gland had a high basal concentration of calcitonin in serum (1.3 ng/ml), and intravenous infusion of calcium increased the serum level of calcitonin more than 8-fold. The surgically removed tumor contained 170 ^× _÷ 1.31 MRC Units of calcitonin per g of tissue. The tumor was placed in tissue culture and release of calcitonin was measured by radioimmunoassay. During the first week in culture a large decrease in the rate of release of calcitonin occurred; calcitonin release then stabilized and remained essentially constant over the next two weeks. Effects of added CaCl₂, MgCl₂» EGTA, glucagon and dibutyryl cAMP were examined after the first week of culture. Added CaCl₂ (20 mM) increased the release of calcitonin about 2-fold while magnesium alone or in combination with calcium had no effect. About 80% reduction in medium [Ca⁺⁺], obtained by addition of EGTA, had no effect on the release of calcitonin; however, glucagon (6 × 10^-6 M) and dibutyryl cAMP (2.5 7times; 10^-4 M) each stimulated the accumulation of calcitonin in medium more than 2-fold. 1 This investigation was supported in part by a grant from the National Institute of Arthritis, Metabolism and Digestive Diseases (AM 10206).