Effect of thyroid hormone on growth. Lessons from the syndrome of resistance to thyroid hormone.

Thyroid hormone deprivation results in deleterious effects on bone growth. The delayed bone development is mediated by a direct effect of thyroid hormone on bone and an indirect effect of the hormone on GH release and IGF-1 action. Both TR alpha and TR beta are expressed in bone cells. To examine the role of TR beta on bone, we have reviewed the growth abnormalities in the human syndrome of RTH caused by mutations in the TR beta gene. The mutant TR beta reduces the tissue responsiveness to thyroid hormone, producing in some tissues variable degrees of thyroid hormone deprivation. With regard to bone, relative thyroid hormone deficiency caused by the mutant TR beta produces short stature and delayed bone growth but does not attenuate growth to the extent that absolute thyroid hormone deficiency does. These observations indicate that an intact TR beta is required for normal bone development and growth.