Triiodothyronine Treatment Research Articles

Metabolic Effects of Infused Sodium L (+) Lactate in Man before and after Triiodothyronine Treatment

AbstractIn untreated subjects infusion of 2.3 mg L(+) lactate per kg per min for 30 min increased the blood lactate concentration by a maximum of 9.4 ± 0.46 mg% and the oxygen consumption by a maximum of 9.5 ± 1.50%. The increase in oxygen consumption was sufficient to oxidize 34% of the infused lactate. After treatment with 1 mg triiodothyronine the increase in the blood lactate concentration was smaller than in the same subject before T3 treatment. The increase in oxygen consumption was greater, on the other hand, and was calculated to be sufficient for complete oxidation of 52% of the infused lactate.

Ribonucleic acid synthesis during the early action of thyroid hormones.

1. The effect on RNA synthesis in rat liver of thyroidectomy and the administration of thyroid hormone, especially during its physiological latent period, was studied by determining: (a) the activity of DNA-dependent RNA polymerase in isolated nuclei; (b) the rate of synthesis of nuclear and cytoplasmic RNA in vivo; (c) polyribosomal sedimentation profiles; (d) the response of microsomes and ribonucleoprotein particles to polyuridylic acid; (e) the effect of inhibitors of RNA and protein synthesis on the biological activity of hormones. 2. The DNA-dependent RNA-polymerase activity of isolated rat-liver nuclei was lowered by thyroidectomy and stimulated by the administration of tri-iodo-l-thyronine or l-thyroxine (2-25mug./100g. body wt.) to both normal and thyroidectomized rats. In thyroidectomized rats, the activity of the Mg(2+)-activated RNA-polymerase reaction (for which the product is mainly ribosomal type of RNA) was stimulated at 10-12hr. after a single injection of tri-iodothyronine, reaching a peak value of 60-90% stimulation at 45hr. after hormone administration. The Mn(2+)/ammonium sulphate-activated RNA-polymerase reaction (for which the RNA product is more DNA-like) was not affected for 24hr. after hormone administration but stimulated by 30-40% at 45hr. The response of both RNA-polymerase reactions to the hormone in vivo paralleled the physiological response but the enzyme was not stimulated by the addition in vitro of the hormone to isolated nuclei. 3. Within 3-4hr. after tri-iodothyronine administration to thyroidectomized rats, the specific activity of rapidly labelled nuclear RNA, after a 10min. pulse of [6-(14)C]orotic acid, was 30-40% greater than the control values, the stimulation reaching 100 and 200% at 11 and 16hr. respectively after hormone administration. Longer exposures to [6-(14)C]orotic acid and [(32)P]phosphate showed that the hormone accelerated the synthesis of mitochondrial, microsomal (or ribosomal) and soluble RNA. The greater part of the labelled nuclear RNA was of the ribosomal type. The hormone-induced increases in the incorporation of radioactive precursors into RNA were not preceded, but followed, by enhanced uptake of the precursor. There was no change, per g. of liver, of DNA, nuclear RNA or soluble RNA, but there was a 40-60% increase in the amount of ribosomal RNA between 35 and 45hr. after a single injection of tri-iodothyronine to thyroidectomized rats. 4. Coinciding with the increase in ribosomal RNA after hormone administration was an increase in the average size and amount of polyribosomes. The newly formed ribonucleoprotein particles, or messenger RNA attached to them, or both, were more firmly bound to microsomal membranes after hormone treatment. 5. Polyuridylic acid caused a bigger stimulation of incorporation of [(14)C]phenyl-alanine by ribonucleoprotein particles, but not by microsomes, from thyroidectomized rats as compared with preparations from normal animals. The response of ribonucleoprotein particles to polyuridylic acid was lowered after tri-iodothyronine treatment of thyroidectomized rats. 6. Actinomycin D, 5-fluorouracil, puromycin and cycloheximide caused a 70-100% inhibition of the stimulatory effect of l-thyroxine and tri-iodo-l-thyronine on basal metabolic rate and growth rate in both normal and thyroidectomized animals. Administration of actinomycin D also abolished the stimulation of RNA polymerase by tri-iodothyronine. 7. It is concluded that regulation of nuclear and ribosomal RNA synthesis is an essential step leading to the biological action of thyroid hormones and that the formation of new ribosomes is an important aspect of the control of cytoplasmic protein synthesis by these hormones.

Thyroid hormone regulation of cardiac glycogen metabolism

The administration of thyroxin to rats (500 μg daily for 2–3 weeks, 500 μg daily for 1 week, or 50 μg daily for 2 weeks) or triiodothyronine (100 μg daily for 3–5 days) increased cardiac phosphorylase a levels. Total cardiac phosphorylase activity was unchanged. Pretreatment with reserpine prevented and the β-adrenergic blocking agents reduced this thyroxin-induced increase in phosphorylase a. Thyroxin or triiodothyronine treatment potentiated the response of cardiac phosphorylase to exogeneously administered catecholamines. This enhancement of the catecholamine-induced increase in phosphorylase a could be clearly demonstrated after the animals were pretreated with reserpine. Dose-response relationships for these agents are illustrated. Glycogen analyses on the same hearts indicated a parallelism between the increase in phosphorylase a and the reduction in glycogen content. While hearts of thyroidectomized animals showed a decrease in phosphorylase a levels and an increase in glycogen relative to controls, the response after catecholamines was unchanged. These data suggest that thyroxin may enhance these catecholamine responses by modulation of the myocardial metabolic adrenergic receptor.

The effect of thyroxine and triiodothyronine treatment on the resin uptake of I 131-thyroxine and triiodothyronine

Healthy volunteers were given 3 week courses of full replacement doses of a thyroid hormone; 4 received 1-thyroxine followed by 1-triiodothyronine and 4 were given only 1-triiodothyronine. Their thyroid I 131 uptakes, serum protein-bound iodines, and resin sponge uptakes of tracer thyroxine and triiodothyronine were measured before and at the end of each treatment period. Thyroid function was suppressed by both treatment regimens. Thyroxine raised the serum protein-bound iodine, while triiodothyronine lowered it. The resin sponge uptakes showed a significant increase during thyroxine therapy, but were not significantly different from the control period at the end of triiodothyronine therapy. The failure of physiologic replacement doses of 1-triiodothyronine to affect the resin sponge uptake test as measured with tracer hormones, was confirmed by an in vitro study.

The turnover of norepinephrine in thyrotoxic and nonthyrotoxic mice

The turnover of administered tritiated norepinephrine (H 3NE) was studied in the hearts of normal mice and mice after daily administration of triiodothyronine. The data show that although the concentration of endogenous norepinephrine (NE) is decreased after triiodothyronine treatment, the total NE content of the heart remains unaltered. These results show that the lowered level of NE results from hypertrophy of the heart muscle. The rate of disappearance of H 3NE is similar in hearts of normal and hyperthyroid animals, indicating that the rate of synthesis of endogenous NE is not affected by triiodothyronine administration. It is concluded that the symptoms of hyperthyroidism cannot be explained on the basis of more rapid formation of NE.

VERLAUFSUNTERSUCHUNGEN DES WASSERHAUSHALTES BEI ADIPÖSEN UNTER TRIJODTHYRONINTHERAPIE MIT BERÜCKSICHTIGUNG DER ALDOSTERONAUSSCHEIDUNG IM HARN UND EINES ANTIDIURETISCHEN PRINZIPS IM SERUM (ADH)

ABSTRACT In 4 patients with excessive obesity (78.4—160.8 kg body-weight) the following determinations were performed before and during triiodo-thyronine treatment: the aldosterone excretion in the urine, the serum concentration of antidiuretic substances (ADH according to Buchborn), the osmolality, sodium, potassium and chloride in plasma and urine, the total and extracellular fluid compartments, the glomerular filtration rate (by inulin clearance), the renal plasma flow, and the circulating plasma volume. During triiodothyronine treatment, the previously increased levels of aldosterone in the urine and the serum ADH decreased towards the normal range. The glomerular filtration rate and the renal plasma flow, both as a rule significantly reduced in obesity, as well as the circulating plasma volume were increased. In all 4 cases, the administration of triiodo-thyronine was followed by distinct natriuresis, reduction of the cholesterol level in the serum, and an increase of the basal metabolic rate. A statistically significant relation could be demonstrated between the aldosterone excretion rate in the urine and the ADH concentration of the serum on the one hand and the circulating plasma volume on the other. This relation was also found between the aldosterone excretion and ADH concentration in the serum.

BIOCHEMISTRY OF AMPHIBIAN METAMORPHOSIS: EFFECT OF TRIIODOTHYRONINE, THYROXIN, AND DINITROPHENOL ON THE RESPIRATION OF THE TADPOLE12

A simple method involving the Warburg apparatus has been used for the study of the oxygen consumption of small and moderate sized tadpoles. Significant increases in the respiration of tadpoles were observed after small doses of 3,5,′-triiodothyronine, regardless of the unit of tissue used for the calculation. Thyroxin also increased tadpole oxygen consumption. However, it was not possible to establish whether or not spontaneous metamorphosis is accompanied by an increase in respiration. The tadpole gave a calorigenic response to 2,4-dinitrophenol whether administered by injection or by immersion. No significant increase was noted in succinoxidase activity after 3,5,′-triiodothyronine treatment. The possibility of the greater importance of alternative paths of oxidative metabolism in the tadpole is suggested.