Thyroid hormone-carbohydrate interaction at the hepatic nuclear level.
We have studied the interaction between triiodothyronine (T3) and carbohydrate (CHO) in the induction of hepatic lipogenic enzymes under both in vivo and in vitro conditions. Our studies demonstrate a synergistic relationship between T3 administration and CHO feeding in the induction of these enzymes. Likewise, in states characterized by CHO deprivation such as starvation and diabetes, the response to T3 is also inhibited. Studies in the aging animal have documented a diminished response both to CHO and to T3. Our studies suggest that T3 multiplies a primary CHO-generated signal by a constant factor, and that this signal declines with age. Additional studies with primary hepatocyte cultures provide evidence that glucose is the main factor responsible for the induction of hepatic malate dehydrogenase: decarboxylating (EC 1.1.1.40) (ME). Glucose induces ME in the absence of changes in extrahepatic hormones or metabolites and in the complete absence of T3. In the cultured hepatocyte system, T3 also acts as a constant multiplier of the primary glucose-derived signal. Our results provide further support for the thesis that the primary action of T3 at the molecular level is a multiplication of other nuclear signals. The complexity of response pattern to both T3 and CHO administration, however, is illustrated by recent studies in which we have analyzed the translated products of total poly(A+) RNA extracted from livers of rats subjected to various physiological stimuli.
D000375:Aging; D000818:Animals; D002241:Carbohydrates / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology; D004790:Enzyme Induction; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005947:Glucose / Q000502:physiology; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis; D007328:Insulin / Q000502:physiology; D050356:Lipid Metabolism; D008099:Liver / Q000502:physiology*; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D010734:Phosphogluconate Dehydrogenase / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011988:Receptors, Thyroid Hormone; D013217:Starvation; D014284:Triiodothyronine / Q000502:physiology*
D002241:Carbohydrates; D007328:Insulin; D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D008291:Malate Dehydrogenase; C031917:malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+); D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D064429:Fatty Acid Synthases; D005947:Glucose