Stable T4 Research Articles

Alterations in thyroid hormone economy during acute infection with Diplococcus pneumoniae in the rhesus monkey.

In order to study the alterations in thyroid hormone economy that accompany an acute bacterial infection, rhesus monkeys were inoculated i.v. with a virulent Diplococcus pneumoniae culture containing approximately 10(8) organisms per dose. This was found to produce a well-defined febrile illness followed in most instances by spontaneous recovery, thereby permitting sequential observations to be made during progression from the healthy state through acute infection into convalescence. During the acute febrile period of the infection, the clearance of both exogenously labeled L-thyroxine (T(4)) and 3,3',5-triiodo-L-thyronine (T(3)) from their peripheral pools was accelerated. This alteration was often evident by 8 hr after inoculation with the virulent culture and could not be ascribed to a decrease in extracellular binding. Despite the accelerated hormonal clearance, the concentrations of both endogenously labeled thyroid hormone and stable T(4) in the sera of the surviving monkeys remained essentially unchanged or increased, indicating that hormonal secretion must have increased during this period. During the convalescent period, hormonal clearance was similar to preinfection control values. Leukocytes isolated from blood obtained 6 hr after inoculation with the virulent culture displayed enhanced T(4)-deiodinative activity.

Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects

Studies of the possibility that thyroxine (T4) is converted to 3.5,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-L-thyroxine.T3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml). These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum. When oral medication was enriched with (125)I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA(4)) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the (125)I-labeled T3 and TA(4) were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA): in contrast the labeled TA(4) was bound by albumin and TBPA, but not by TBG. To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administration, the sera of two additional patients were obtained 48 hr after 7-day courses of daily intravenous injections of a mixture of stable and (125)I-labeled T4. Both stable and labeled T3 were likewise found in these sera. In contrast to earlier experiments in humans in which (131)I-labeled T3 was not definitively demonstrated in serum after a single intravenous injection of (131)I-labeled T4, the present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man. These results raise once again the question of the extent to which the metabolic effect of T4 is mediated through the peripheral generation of T3.

Effect of epinephrine on the peripheral metabolism of thyroxine

10 normal young men received repository epinephrine repeatedly for 4 days during the course of a radiothyroxine (radio-T4) disappearance curve. During epinephrine administration, serum radio-T4 disappearance rate (k) slowed abruptly, fecal clearance decreased, urinary clearance was initially unchanged but later decreased slightly, volume of thyroxine distribution decreased, and external radioactivity over the liver remained unchanged. Beginning on day 2 of epinephrine and persisting at least 1 day after epinephrine was discontinued, serum thyroxine-binding globulin (TBG) maximal binding capacity increased, thyroxine-binding prealbumin (TBPA) maximal binding capacity decreased, and free T4 iodine decreased. Stable serum T4 iodine decreased during the experiment. Three indexes, namely the free T4 iodine, the reciprocal of TBG capacity, and the urinary radio-T4 "clearance" changed in parallel, suggesting that the increase in TBG capacity was responsible for a delayed decrease in radio-T4 metabolism. However, these changes were temporally dissociated from the decrease in k, which began and ended abruptly with initiation or discontinuing of epinephrine administration. This dissociation is unexplained, but may be caused by alterations in T4 binding in tissue sites.

Factors affecting exchange of thyroid hormones between liver and blood.

Radioactively labeled thyroxine was administered to rats, and after 1 to 20 hr their livers were isolated and perfused with pooled rat blood. It was found that, during the perfusion, unchanged T4 was released to the perfusing blood. The efflux of T4 from liver to blood was decreased by the addition of sodium salicylate to the perfusing blood and was reversed by the addition of 2 mg of stable T4 to the perfusate. When T4 in liver and blood had approached an equilibrium, exchange transfusion resulted in a further efflux of T4 from the liver and the establishment of a new equilibrium. The dynamic equilibrium existing between T4 in liver and in blood was shown most dramatically when T4- 131I was in the liver and T4-125I was in the blood when perfusion of the liver began. Livers from rats given radioactively labeled triiodothyronine (T3) released only a small amount of T3 to the perfusing blood but deiodination and conjugation were greater than after administration of T4-131I. (Endocrinology 79: 391, 1966)

Effect of thyrotrophic hormone on thyroxine uptake by abdominal muscle of mouse.

By in vitro study with surviving abdominal muscle of mouse, an enhancing effect of TSH on uptake of I131-labeled Lthyroxine (T4) was demonstrated. Muscle pieces were incubated in Krebs-Ringer phosphate solution containing I131-T4. The T4- binding capacity proved to be smaller in tissue from TSH-injected mice, and larger in tissue from T4-injected mice, than in muscle taken from control animals. However, the rate at which T4 uptake approached maximal was the same in all treatment groups. These results suggest that T4 uptake by peripheral tissue in vivo is not always increased by a rise in circulating T4 level. The decrease in the binding capacity of tissue from TSH-treated mice is ascribed to a decrease in the number of intracellular T4-binding sites in vivo, due to increased uptake of T4. Results obtained in experiments involving preincubation of muscle tissue with stable T4 or TSH confirmed that the decrease in binding capacity was due to the partial presaturation of the intracellular T4-binding sites wi...