GLUCAGON INFLUENCES THE EXPRESSION OF THYROID-HORMONE ACTION - DISCREPANCY BETWEEN NUCLEAR TRIIODOTHYRONINE RECEPTOR NUMBER AND ENZYME RESPONSES

Studies were undertaken to evaluate the influence of elevated plasma glucagon on the maximal nuclear T3[triiodothyronine]-binding capacity (MBC) and the expression of thyroid hormone action. Infusion of 1 .mu.g glucagon/100 g BW [body wt] .cntdot. h for 16-65 h led to plasma glucagon levels of 990 .+-. 110 pg/ml from baseline levels of 248 .+-. 32 pg/ml. This degree of increase in plasma glucagon has been reported to occur in hepatectomized and starved animals [rats]. The maximal nuclear binding capacity was decreased by approximately 30% within 17-65 h after the start of the glucagon infusion. Administration of 0.5 mg T3/100 g BW 41 h after the start of the glucagon infusion led to a normal rise in .alpha.-glycerophosphate dehydrogenase over the subsequent 24 h. The response of malic enzyme, however, was completely inhibited. Infusion of 5 .mu.g glucagon/100 g BW .cntdot. h resulted in a fall in the MBC to 46% of control values 17 h after the start of the infusion. Despite continuation of the infusion, the MBC returned to near normal values at 41 h (MBC, 86% of control) and at 65 h (MBC, 89% of control). Administration of 0.5 mg T3/100 g BW at 41 h failed to elicit a response of malic enzyme at 65 h despite an insignificant depression in MBC. Glucagon levels of about 5500 pg/ml were maintained throughout the experiment. In addition, malic enzyme induction by T3 was completely inhibited by the infusion of 0.5 .mu.g glucagon/100 BW .cntdot. h despite the failure to elicit a significant lowering of MBC at any time. Inhibition of the response of malic enzyme to T3 in the presence of near-normal MBC suggests that glucagon inhibits the effects of T3 at a point beyond the nuclear receptor. The decrease in MBC and the inhibition of induction of malic enzyme previously described in hepatectomized and starved animals may be mediated by glucagon.