Interrelationship of triiodothyronine concentration, metabolism, protein binding, and nuclear occupancy in the induction of malic enzyme by cultured adult rat hepatocytes.

Abstract

We have previously demonstrated the utility of the cultured adult rat hepatocyte system for the study of the induction of malic enzyme by T3. Although such induction could be demonstrated with medium both containing and lacking serum proteins, we noted that an 11-fold higher initial free T3 concentration was required to achieve a given level of enzyme induction when serum was absent from the medium. Since it appeared possible that this phenomenon might be related to an accelerated rate of T3 metabolism in the absence of serum, we undertook a theoretical and experimental analysis to assess the effect of reversible serum binding on both the rate of T3 metabolism and the rate of malic enzyme generation. We developed a mathematical model based on the provisional assumption that the medium proteins act exclusively through the reversible binding of T3. This allowed us to predict a number of parameters of metabolism and distribution as a function of serial protein dilution. Thus, as predicted by the model, seria...