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Glucagon Influences the Expression of Thyroid Hormone Action: Discrepancy between Nuclear Triiodothyronine Receptor Number and Enzyme Responses^*

WOLFGANG H. DILLMANN and JACK H. OPPENHEIMER

Division of Endocrinology and Metabolism, Department of Medicine, University of Minnesota Minneapolis, Minnesota 55455

Address requests for reprints to: Dr. Jack H. Oppenheimer, Department of Medicine, Mayo Box 91, University of Minnesota, Minneapolis, Minnesota 55455.

Abstract

Studies were undertaken to evaluate the influence of elevated plasma glucagon on the maximal nuclear T₃- binding capacity (MBC) and the expression of thyroid hormone action. Infusion of 1 µg glucagon/100 g BW-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. 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 a-glycerophosphate dehydrogenase over the subsequent 24 h. The response of malic enzyme, however, was completely inhibited. Infusion of 5 µg glucagon/100 g BW-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 infusio, 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 in spite of 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 µg glucagon/100 g BW-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 nearnormal MBC suggests that glucagon inhibits the effects of T₃ at a point beyond the nuclear receptor. Our findings also raise the possibility that the decrease in MBC and the inhibition of induction of malic enzyme previously described in hepatectomized and starved animals are mediated by glucagon.

Footnotes

^* This work was supported by NIH Grant AM-19812-3.

Recipient of Research Career Development Award 7K04HL00315- 03. Present address: University Hospital, Department of Medicine, 225 W. Dickinson Street, San Diego, California 92103.

Received November 20, 1978.