Responses of Fetal Rat Bone to Thyrocalcitonin in Tissue Culture

The effects of partially purified rat thyrocalcitonin (TCT) on fetal rat bone were investigated in organ culture using a system sensitive to the resorbing effects of parathyroid hormone (PTH) and vitamin A. Effects on resorption were measured by the changes observed in release of previously incorporated 45Ca into the medium from paired cultures. TCT decreased 46Ca release in untreated as well as PTHor vitamin A-stimulated cultures, but had no effect on 45Ca release from heat-killed bone. The dose-response relation for TCT inhibition of 45Ca release was the same for PTH- or vitamin Atreated bones. Increasing doses of PTH did not overcome the inhibitory effect of a submaximal dose of TCT. Addition of liver, salivary gland or pituitary gland extracts in amounts comparable to an effective dose of thyroid extract did not affectaffect bone resorption. TCT suppressed further PTH-stimulated 45Ca release for about 48 hr when added 6, 12 or 24 hr after PTH. However, with periods of 4–6 days of combined treatment with PTH and TCT, 45Ca release began to increase again and was accompanied by characteristic histologic changes of the PTH effect. This increase in 46Ca release due to “escape” was somewhat less with TCT continuously present than that observed with “recovery” when TCT was removed after 48 hr from PTH-treated bones. The data indicate that TCT is a potent inhibitor of bone resorption with a limited duration of action. TCT can temporarily overcome the effects of PTH but does not appear to compete for the same site of action. (Endocrinology82: 149, 1968)