A B S T R A C T As judged from both paper and column chromatography, slices or homogenates of liver from rats fasted for 48 h displayed a lesser rate of generation of 1251-labeled 3,5,3'-triiodothyronine (T3) from 1251-labeled thyroxine (T4) added to incubation media than did preparations from normal chow-fed animals. A similar defect in the conversion of T4 to T3 in the livers of fasted animals was observed when preparations were incubated with substrate concentrations of T4 so that T3 generation could be assessed by radioimmunoassay. The effect offasting could be prevented, wholly or in part, by administration of glucose in the drinking water to otherwise fasted animals, and the degree ofprevention appeared to be proportional to the concentration of glucose employed. Diminished generation of T3 from T4 was similarly evident in the livers of animals with streptozotocin-induced diabetes mellitus, and this defect was overcome by the provision of insulin in vivo, but not in vitro. Decreased formation of T3 from T4 was also observed in preparations of liver from animals given dexamethasone, amiodarone, and propylthiouracil. In no case could these effects on the net formation of T3 from T4 be explained by effects of the experimental conditions on the degradation of the T3 generated, as judged from the rate of degradation of exogenous 125I-T3 measured in parallel incubates.An analysis of the rate of disappearance of 125I-T4 from reaction mixtures in relation to the rate of appearance of 125I-T3 and 1251-iodide was employed to estimate the activity of the 5-monodeiodinating pathway of T4 metabolism that leads to the formation of 3,3',5'-triiodothyronine (reverse T3). Such estimates indicated that reverse T3 formation was actively proceeding in the preparations studied, was slightly enhanced by Received for publication 9 November 1977 and in revised form 14 March 1978. fasting, was unaffected by dexamethasone and amiodarone, and was markedly inhibited by propylthiouracil.In view ofthe similarities between the effect ofthese experimental manipulations on the generation of T3 from T4 by rat liver in vitro to their effects on the production rates and serum concentrations of T3 in man, it is concluded that the rat liver system provides a suitable model for the study of factors that influence the conversion of T4 to T3 in man. In addition, the findings strongly indicate that this process, at least in the liver, is closely linked to the utilization of carbohydrate. INTRODUCTION Recent studies have provided convincing evidence that 3,5,3'-triiodothyronine (T3)l contributes a major portion to the overall metabolic action of the thyroid hormones within the peripheral tissues. It is evident, moreover, that much of the T3 found in the blood of normal man arises, not by direct secretion from the thyroid gland, but rather from the peripheral monodeiodination of thyroxine (T4) in its outer ring at the 5'-position. It is generally agreed that this reaction results in activation of the hormone molecule, as T3 is several times more ...
