Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells

T-4, which is a major secretory product of the thyroid gland, needs to be c onverted to T-3 by iodothyronine deiodinase to exert its biological activit y. After the molecular cloning of human type II iodothyronine deiodinase (D II) complementary DNA, DII expression was unexpectedly detected in human sk eletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscl e cells and studied the mechanisms involved in the regulation of DII expres sion in those cells. All of the characteristics of the deiodinating activit y in cultured human skeletal muscle cells were compatible with those of DII . Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)(2)cAMP, forskolin, or beta-adre nergic agonists and were negatively regulated by thyroid hormones in cultur ed human skeletal muscle cells. Although interleukin-1 beta and interleukin -6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-cu decreased DII expression in those cells in a dose -dependent manner. These data have demonstrated, for the first time, that D II activity and DII mRNA are present in cultured human skeletal muscle cell s, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid horm ones and tumor necrosis factor-alpha.