Effect of decreased hepatic nuclear l-triiodothyronine receptors on the response of hepatic enzymes to ltriiodothyronine in tumor-bearing rats

The activity of hepatic α-glycerophosphate dehydrogenase (α-GPD) and malic enzyme (ME) was measured in rats bearing the Walker 256 carcinoma to assess the relationship between the reduction in the nuclear L-T₃ (T₃) receptor concentration which occurs in tumor-bearing (T) rats and the biological effects of thyroid hormones. T₃ receptor concentration was uniformly decreased when tumors exceeded 9.5% of body weight. No change in basal α-GPD activity was observed, but ME activity was decreased to between 29–61% of control. The decrease in ME activity did not appear to be related to decreased nuclear T;) receptor concentration since ME was also decreased in T rats with tumors that were too small to effect a decrease in the concentration of nuclear T₃ receptors or plasma T₄ and T₃. The response of both ME and α-GPD to T₃ administration in T rats was comparable to that of control despite reduced nuclear T₃ receptor and plasma hormone concentrations. When non-T rats were subjected to food restriction to simulate the attenuated growth curves of T rats, no changes were observed in nuclear T.t receptor concentration, plasma T₄ and T₃ concentration, or basal activity of a-GPD or ME. The induction of two thyroid hormonesensitive hepatic enzymes in rats with reduced nuclear T₃ receptor and plasma T₃ concentrations suggests that nuclear receptors are lost from sites which are not involved with the regulation of α-GPD or ME. Thus, unchanged receptor levels at sites which control α-GPD and ME may lead to normal biological responses of these enzymes despite reduced total receptor concentration.