Thyrocalcitonin and bone resorption: Studies employing a tissue culture bioassay

Thyrocalcitonin, partially purified from rat thyroid glands, is a potent inhibitor of resorption in tissue cultures of fetal rat bone. This inhibition is best demonstrated when resorption is stimulated by parathyroid hormone, but can occur independently. The ability of thyrocalcitonin to block bone resorption stimulated by parathyroid hormone in tissue culture has provided a sensitive, specific and reproducible bioassay which can be used to detect thyrocalcitonin-like activity in serum. The results of this bioassay indicate that the serum of thyroid-intact rats contains an inhibitor of bone resorption which appears after a hypercalcemic stress. The amount of thyrocalcitonin activity was similar in parathyroidectomized rats, which required injections of large amounts of calcium to increase their serum calcium concentration from low to hypercalcemic values, and rats with parathyroid transplants which required only small amounts of calcium to increase their serum calcium concentration from normal to similar hypercalcemic values. Thyrocalcitonin-like activity could not be demonstrated in the serum in the absence of a calcium stress. Prolonged administration of thyrocalcitonin in tissue culture results in an escape of the bone from its inhibitory effect and the resumption of active bone resorption in the presence of parathyroid hormone and thyrocalcitonin. This escape phenomenon was due to the continuous presence of partially purified thyrocalcitonin and not to any changes in the cells during tissue culture or to the presence of parathyroid hormone. The data fit the hypothesis that thyrocalcitonin is an emergency hormone secreted only intermittently in response to hypercalcemic stress. Its action is to inhibit bone resorption, resulting in a decrease in the movement of calcium from bone to blood and a lower serum calcium concentration.