Tissue iodoprotein formation during the peripheral metabolism of the thyroid hormones

The formation of tissue iodoproteins during the peripheral metabolism of the thyroid hormones was examined by determining the concentration of nonethanol-extractable (125)I (NE(125)I) in various tissues after the intravenous injection of 3,5,3'-triiodo-L-thyronine (T3-(125)I) and L-thyroxine-(125)I (T4-(125)I) in groups of rats with iodide-blocked thyroid glands. 3 days after T3-(125)I and 7 days after T4-(125)I injection the concentration of NE(125)I in the liver and kidney was 5-10 times greater than in plasma. Smaller but nonetheless significant concentrations of NE(125)I were demonstrated in skeletal and cardiac muscle. Hepatic subcellular fractionation studies revealed that the major portion of the liver NE(125)I was in the microsomal fraction. Lower concentrations of NE(125)I were present in the nuclear, mitochondrial, and soluble fractions. When similar studies were performed in groups of rats pretreated with phenobarbital, an increase in the metabolic clearance of T3-(125)I (30%) and T4-(125)I (100%) was observed along with a highly significant increase in the NE(125)I concentration of the liver and plasma. The increase in hepatic NE(125)I in these studies was primarily due to the microsomal component. Incubation of hepatic microsomes with T3-(125)I and T4-(125)I showed that NEI formation as well as deiodination appeared to obey simple Michaelis-Menten kinetics. Moreover, the maximal rate of both deiodination and NEI formation was increased when microsomes harvested from phenobarbital-treated rats were employed. These studies indicate that thyroid hormone metabolism results in the formation of structural and soluble tissue iodoproteins in addition to circulating iodoproteins. The rate of formation of these moieties in the liver and plasma appears to be related to the rate of hormone metabolism.