Cyclic AMP and Thyroid Hormone: Inhibition of Epiphyseal Cartilage Cyclic 3′,5′-Nucleotide Phosphodiesterase Activity by L-Triiodothyronine

Abstract

Summary

The mechanism for the alteration in cartilage growth and metabolism present both in childhood thyroid hormone deficiency states and in hyperthyroid children has not been defined. Since thyroid hormone has a direct effect on the adenylate cyclase-cyclic 3′,5′-nucleotide phos-phodiesterase system in certain tissues, the effect of thyroid hormones on soluble cyclic 3′,5′-nucleotide phosphodiesterase (PDE) activity prepared from chicken epiphyseal (growth) cartilage was examined. L-Triiodothyronine at a concentration of 1 × 10⁻⁴ M resulted in 69% inhibition of soluble cartilage cyclic 3′,5′-nuc-leotide phosphodiesterase activity. At identical concentrations L-thyroxine, D-thyroxine, D-triiodothyronine, and L-diiodothyronine demonstrated only 42, 41, 38, and 20% inhibition of phosphodiesterase activity, respectively. The concentration of L-triiodothyronine that resulted in 50% inhibition of phosphodiesterase activity was 3.5 × 10⁻⁵ M. This investigation demonstrates a significant inhibitory effect of L-triiodothyronine on cartilage 3′,5′-nucleotide phosphodiesterase activity, whereas other thyroid analogs tested were considerably less active as inhibitors of this enzyme. These findings suggest that cyclic nucleotide metabolism may be involved in regulating the effects of the most potent thyroid hormone, L-tri-iodothyronine, on epiphyseal cartilage.

This investigation was supported in part by National Institutes of Health Grant No. R01 AM 16151 and an Arthritis Clinical Research Center Grant.