Total thyroidectomy in the management of thyrotoxic and euthyroid Graves' disease.
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The role of adenine nucleotide translocase (AdNT) in the reduced oxidative metabolism of hypothyroidism has been examined. Both AdNT and respiratory activities in liver mitochondria of thyroidectomized rats were 30% below normal. Mitochondrial AdNT activities were determined by the back-exchange method of Pfaff and Klingenberg (Eur. J. Biochem. 6, 66, 1968). The Km and Vmax of the enzyme were temperature dependent. At physiological temperature, the Km and Vmax of the normal rat AdNT were 10 microM (for external ADP) and 4.73% s-1 (percentage efflux of the labeled adenine nucleotides), respectively. AdNT in hypothyroid rat liver mitochondria exhibited a 25-35% lower Vmax and 75% higher Km when assayed over the temperature range 0 to 37 degrees C. Dixonplot studies indicated that the AdNT in hypothyroidism was two- to threefold more sensitive to atractylate and palmitoyl-CoA inhibitions. In contrast the ADP-ATP translocase in hypothyroidism was more resistant than the control carrier to bongkrekate inhibition. The decrease in the transport of ADP, which is consistent with the decreased oxidative activity associated with hypothyroidism, apparently occurs secondary to changes in the lipid matrix of the inner mitochondrial membrane (F. L. Hoch (1977) Arch. Biochem. Biophys. 178, 535.).
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We have isolated and characterized cDNAs representing the rat thyrotropin-beta-subunit. The cDNAs were prepared from poly(A)+ RNA obtained from rat pituitary glands and encode the precursor of the rat thyrotropin-beta-subunit which contains a leader or signal peptide of 20 amino acids, and an apoprotein of 118 amino acids. Blot hybridization analysis of total rat liver DNA digested with several restriction enzymes indicates the likelihood of a single gene encoding the rat thyrotropin-beta-subunit. In addition, analyses of pituitary RNA from normal and thyroidectomized rats indicate that the mRNA encoding the rat thyrotropin-beta-subunit is approximately 700 bases in length and its level increases 8--10-fold after thyroid gland ablation.
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