Experimental Hyperthyroidism Research Articles

Determination of femur structural properties by geometric and material variables as a function of body weight in rats

Since thyroid hormone accelerates energy-requiring processes, a negative caloride balance often exists in the hyperthyroid state. To assess the role of this induced calorie deficit in the production of thyrotoxic myopathy, we have examined the effect of calorie deprivation on creatine excretion in experimental hyperthyroidism. Since food restriction decreases fecal excretion of thyroid hormone, a low-residue glucose-supplemented diet has been used to produce calorie-replete hyperthyroid animals having circulating thyroid hormone levels comparable to half-starved hyperthyroid animals. Calorie-deprived hyperthyroid animals have a 2–4-fold increase in creatine excretion when compared to fully fed hyperthyroid animals having comparable thyroid hormone levels. Although a negative calorie balance greatly enhances creatinuria in experimental hyperthyroidism, it is not a necessary condition for thyroid hormone-induced creatinuria. Calorie-replete hyperthyroid animals consistently gained weight, indicating a positive calorie balance. Nevertheless, these animals manifested increased creatinuria when compared to euthyroid controls. Therefore, excess thyroid hormone appears to cause muscle damage as reflected in creatinuria by a mechanism other than mobilization of muscle protein to provide endogenous calories. A study of the effect of triiodothyronine (T3) on creatine and urea excretion in fasting rats led to the same conclusion. T3 plus fasting produced a much more marked creatinuria than fasting alone. During the first 48 hr of fasting, the rate of weight loss and urea excretion were comparable in T3-treated and control animals. Nevertheless, the rate of creatine excretion during this interval was 10–12-fold increased in the T3-treated group. In these experiments, there was clearly a dissociation between T3 stimulation of urea excretion and the magnitude of creatinuria induced. Although a negative calorie balance appears to hasten the development of thyrotoxic myopathy, accelerated muscle proteolysis to supply an induced calorie deficit is not an adequate model to account for muscle involvement in hyperthyroidism.

Influence of experimental hyperthyroidism on insulin action in growing sheep

The effects of moderate hyperthyroidism on insulin action were studied in five growing sheep (42 kg live weight [LW]) by the euglycemic hyperinsulinemic clamp technique, with insulin infused at rates of 0.33, 1.00, and 6.00 mU/kg LW/min over successive 2-hour periods. Animals were injected with saline (control) or thyroxine (15 μg/kg LW/d) for 21 days and measurements performed during the final 7 days of each period. Thyroxine (T 4) treatment elevated plasma T 4 less than threefold and plasma triiodothyronine (T 3) twofold. T 4 treatment elevated basal plasma glucose concentration ( P < .01) and insulin metabolic clearance rate at the highest rate of insulin infusion ( P < .05). The maximal insulin-induced increase in glucose metabolic clearance rate (responsiveness) was unaffected by T 4 treatment, but the insulin concentration for a half-maximal response (sensitivity) was lowered during T 4 treatment (122 v 58 μU/mL, P < .05). Insulin infusion failed to completely suppress endogenous glucose output; T 4 treatment had no effect. Insulin caused dose-dependent reductions in circulating concentrations of α-amino N, alanine, d-3-hydroxybutyrate, and glycerol, but not nonesterified fatty acids (NEFA). T 4 treatment increased the sensitivity and responsiveness of α-amino N and alanine concentrations to insulin, the sensitivity of d-3-hydroxybutyrate (all P < .05), and the responsiveness of glycerol to insulin ( P < .01). Thus moderate hyperthyroidism in growing sheep modifies the ability of insulin to regulate metabolism.

Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.

Cardiac changes in experimental hyperthyroidism in dogs

Injection of triiodothyronine (T3) (1 mg/kg per day subcutaneously for 14 days) to 10 healthy dogs produced a hyperthyroid state characterised by high serum T3 concentrations, hypokalaemia, hyperactivity, loss of weight, diarrhoea and thirst. Electrocardiographic measurements showed that these dogs had an increase in heart rate of 63 +/- 11 beats/min with a significantly increased T wave amplitude without changes in R wave amplitude. Echocardiographic measurements showed no changes in fractional shortening and no evidence of ventricular hypertrophy, in contrast to reports in humans, cats and rats. However, the smooth muscle of the coronary arteries was markedly hypertrophied, which may cause a decrease in myocardial perfusion.

Significance of cation transport in control of energy metabolism and thermogenesis.

Significance of cation transport in control of energy metabolism and thermogenesis.

Competitive control of myosin expression: hypertrophy vs. hyperthyroidism

The competition between two opposing influences on the phenotypic expression of skeletal muscle myosin were studied to determine which was the dominant regulator. Experimental hyperthyroidism, which induces fast myosin expression, was produced by subcutaneous implantation of a 40-day constant-time-release triiodothyronine pellet. Compensatory hypertrophy, which induces slow myosin expression, was produced by surgical removal of a synergistic hindlimb muscle. Hyperthyroidism increased the percentage of type II fibers and the fast myosin isoforms in both the plantaris and soleus muscles. Hypertrophy significantly increased the percentage of type I fibers and the slow myosin type in the plantaris and soleus muscles. However, with the simultaneous introduction of hyperthyroidism and hypertrophy, only the hyperthyroid effects were observed. Hyperthyroidism and not physiological demand was found to be the dominant regulator of skeletal muscle myosin expression.

Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat

In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state.

Skeletal muscle glucose disposal after re-feeding in the hyperthyroid rat

Experimental hyperthyroidism has been demonstrated to influence insulin-stimulated glucose utilization in isolated skeletal muscle preparations from fed or starved rats, with increased glycogen-glucose < 1 -phosphate cycling [ I ] and diversion of carbon from net glycogenesis (storage) to glycolysis (degradation) [2]. The present study investigated whether this effect of hyperthywidism is also observed in the intact animal under physiological conditions associated with hyperinsulinaemia and skeletal muscle glycogen deposition, namely refeeding after prolonged (48 h) starvation. Effects of experimental hyperthyroidism o n concentrations of fructose 2,6-bisphosphate [Fru( 2,6)P2], an allosteric activator of glycolysis, were also examined. Two representative hindlimb skeletal muscles: soleus (type 1, oxidative, working in the resting state) and gastrocnemius (type 2. mixed oxidative/ glycolytic. non-working in the resting state), were chosen for study. Comparison was made with changes in glycogen and Fru( 2,6)/’, concentrations in the heart, which is known to exhibit profound changes in contractile activity and metabolism in hyperthyroidism. Albino Wistar rats were either starved for 48 h or starved for 48 h and then refed chow (52% carbohydrate; 16%) protein: 2% lipid, w / ~ ) ud lihitirm, sampling after 2. 4, 6, X or 24 h of refeeding. One group o f rats was injected with triiodothyronine (100 d 6 mg/ 100 g body wt.). Glycogen and Fru( 2,6)P2 concentrations were measured in extracts of freeze-clamped muscles as described previously [4]. Basal (48 h starved) glycogen concentrations were significantly lower in the soleus than in the gastrocnemius, whereas Fru( 2,6)P, concentrations were higher in soleus (compare Figs. l a and lh) . Hyperthyroidism had no effect on basal (48 h starved) glycogen or Fru(2,6)Pz concentrations in either skeletal muscle (Figs. 1 a and 1 h). The initial rate of glycogen repletion was significantly higher in the soleus than in the gastrocnemius (compare Figs. I u and 1 h). This is likely to be related to the significantly lower basal glycogen concentration which is observed in the

Oxidative muscular injury and its relevance to hyperthyroidism

In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical-mediated injury.

Intestinal motor activity in experimental hyperthyroidism in conscious dogs

The small intestinal motor effects of experimental hyperthyroidism were studied in 8 conscious dogs to reveal possible mechanisms of accelerated small bowel transit in hyperthyroidism. Six strain gauge transducers were implanted on the small intestine of each dog. Long-term hyperthyroidism was induced by subcutaneous administration of 100 and 200 μg/kg · day of thyroxin. Application of thyroxin did not interrupt the cyclic fasting motor activity. Thyroxin (100 μg/kg · day) caused a slight increase in the period of the migrating motor complex (p < 0.05). The maximum contractile frequency rose dose-dependently up to 11% (p < 0.05). During phase 2 and the digestive state the contraction frequency increased up to 29% and 27%, respectively (p < 0.05). More contractions occurred in groups during the digestive state in hyperthyroidism. Half of the dogs showed giant migrating contractions during thyroxin administration, whereas those contractions were not observed during the control period. We conclude that fasted and postprandial intestinal motility is changed in experimental hyperthyroidism. Acceleration of small bowel transit may be caused by changes in contractile pattern of phase 2 and the digestive state or by the increased frequency of giant migrating contractions.

Exogenous Triiodothyronine Lowers Thyrotropin-Releasing Hormone Concentrations in the Specific Hypothalamic Nucleus (Paraventricular) Involved in Thyrotropin Regulation and also in Posterior Nucleus

Recent evidence indicates that thyroid hormones can regulate thyrotropin secretion in vivo in part by inhibiting thyrotropin-releasing hormone (TRH) secretion itself. Therefore, to explore whether triiodothyronine (T3) interacts with the specific hypothalamic area involved in thyrotropin (TSH) secretory regulation, the paraventricular nucleus (PVN), Palkovitz micropunches from eight nuclear regions were obtained from 1,000-microns frozen coronal brain slices for immunoassay determinations of TRH. Rats were treated either with parenteral L-T3 for 6 days to induce experimental thyrotoxicosis, or 0.15 M saline. The induction of thyrotoxicosis was confirmed by demonstrating that mean plasma TSH concentrations fell from 108 to less than 10 microU/ml (p less than 0.01). TRH concentrations in the PVN were reduced concomitantly after L-T3 from 1.9 to 1.1 ng/mg protein (p less than 0.05). No reductions in TRH concentrations during T3 treatment occurred in other nuclear groupings except in the posterior hypothalamic nucleus. Total TRH content in the median eminence declined also in T3-treated animals from 1.77 to 1.29 ng, representing a 32% reduction (p less than 0.01). No significant change was seen in the median eminence content of the TRH structurally related dipeptide, cyclo(His-Pro). The data herein indicate that experimental thyrotoxicosis in the rat is associated with a selective reduction in TRH concentrations in the PVN, documenting T3 effects upon hypothalamic TRH metabolism per se.

Kinetics of drug action in disease states. XXXI. Effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine (oxazepam) in rats.

This investigation was designed to determine the effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine and on the binding characteristics of the benzodiazepine receptor complex. Rats were made hyperthyroid by subcutaneous implantation of slow release pellets containing L-thyroxine. This treatment produced the characteristic symptoms of hyperthyroidism: increased serum thyroxine concentrations, increased heart weight and body temperature, and decreased serum protein concentrations. The hyperthyroid rats and a parallel group of normal animals (with drug-free pellets implanted subcutaneously) were slowly infused intravenously with oxazepam until they lost their righting reflex. The hyperthyroid rats required a significantly larger dose of the benzodiazepine and their total serum and cerebrospinal fluid concentrations of oxazepam (but not the serum concentration of free drug and the brain concentration) at the onset of loss of the righting reflex were modestly but statistically significantly lower than those of the normal rats. The receptor density and affinity for diazepam in hyperthyroid rats were not significantly different from those of the normal animals. Hyperthyroidism apparently affects the pharmacokinetics of oxazepam but has, at best, only a small effect on the pharmacodynamics (hypnotic activity) of the drug.

Influence of experimental hyperthyroidism on blood and myocardial serotonin in rats.

Recent reports suggest a role for serotonin in the pathogenesis of primary hypertension and left ventricular (LV) hypertrophy. In this study, we have induced LV hypertrophy by oral feeding of thyroxine at increasing dosages (150-450 micrograms/kg b.wt.) over a 5-week period. The effects of hyperthyroidism on cardiovascular parameters, blood and myocardial serotonin concentrations were assessed. Water-fed rats and formerly hyperthyroid recovered animals served as controls. Thyroxine caused a significant LV hypertrophy: hyperthyroid rats 2.19 +/- 0.16*; controls 1.65 +/- 0.13 g/kg b.wt. (mean +/- SD; *P less than 0.05). An almost complete regression of LV hypertrophy occurred in the recovery group (1.66 +/- 0.20 g/kg b.wt.) 3 weeks after cessation of thyroid hormone application. Thyroxine-treated animals showed a significant increase of serotonin blood levels (thyroxine rats: 2108 +/- 781*, recovery: 1132 +/- 726, controls: 705 +/- 480 ng/ml; *P less than 0.05). The concentrations of serotonin in left ventricular myocardium were increased after thyroid hormone application, whereas the highest levels were found in the recovery group (thyroxine rats: 139.1 +/- 30.4, recovery: 167.2 +/- 43.1, controls: 68.9 +/- 27.9 mg/ml homogenate). Serotonin-containing cells in the left ventricular myocardium were stained immunohistochemically. They were localized perivascularly and were assumed to represent tissue mast cells. In experimental hyperthyroidism the serotonin levels in blood and heart are increased possibly indicating an interaction of both hormones in thyroxine-induced cardiomyopathy.

Effects of hyperthyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat

1. The effects of hyperthyroidism on the sensitivity and responsiveness of glycolysis and glycogen synthesis to insulin were investigated in the isolated incubated soleus muscle of the rat. 2. Hyperthyroidism, which was induced by administration of tri-iodothyronine (T3) to rats for 2, 5 or 10 days, increased fasting plasma concentrations of glucose, insulin and free fatty acids. 3. Administration of T3 for 2 or 5 days increased the rates of glycolysis at all insulin concentrations studied: this was due to increased rates of both glucose phosphorylation and glycogen breakdown, but there was no effect of T3 on the sensitivity of glycolysis to insulin. However, administration of T3 for 10 days increased the sensitivity of the rate of glycolysis to insulin. 4. The concentration of adenosine in the gastrocnemius muscles of the rats was not different from controls after 5 days, but it was markedly decreased after 10 days of T3 administration. If these changes are indicative of changes in the soleus muscle, the increased sensitivity of glycolysis to insulin found after 10 days' T3 administration could be due to the decrease in the concentration of adenosine. 5. Administration of T3 decreased the sensitivity of glycogen synthesis to insulin and the glycogen content of the soleus muscles. This may explain the decreased rates of non-oxidative glucose disposal found in spontaneous and experimental hyperthyroidism in man. 6. The rates of glucose oxidation did not change after 2 days, but they were increased after 5 and 10 days of T3 administration.

Metabolism of plasma fibronectin in rabbits with experimental hyperthyroidism and hypothyroidism

We previously reported that the concentration of plasma fibronectin (pFN) is increased in patients with hyperthyroidism and decreased in those with hypothyroidism. In this work, labeled pFN was given intravenously to euthyroid, hyperthyroid, and hypothyroid rabbits to examine its metabolism in states of thyroid dysfunction. In euthyroid rabbits, the serum concentration of thyroxine (T 4) was 2.94 ± 0.59 μg/dL, and that of pFN was 24.2 ± 1.2 mg/dL. With 125I-FN as tracer, the half life was estimated as 72.8 ± 2.6 hours, the fractional catabolic rate (FCR) as 2.08 ± 0.07%/h, the rate of synthesis (SR) as 3.84 ± 0.20 mg/kg/day and j 1 j 2 (the ratio of the exchange coefficients between intravascular and extravascular compartments) of pFN as 0.295 ± 0.051. With 3H-FN as tracer, these values were not significantly different. In hyperthyroid rabbits, obtained by treatment with l-thyroxine, the serum T 4 concentration was increased to 5.73 ± 1.58 μg/dL and the pFN concentration to 29.6 ± 2.2 mg/dL. In these animals, the half life of pFN was shortened to 59.8 ± 1.0 hour, the FCR was slightly increased to 3.07 ± 0.52%/h and the SR was greatly increased to 7.13 ± 1.17 mg/kg/d. In hypothyroid rabbits, obtained by treatment with methylthiouracil, the serum T 4 and pFN levels were reduced to 1.50 ± 0.36 μg/dL and to 20.7 ± 1.7 mg/dL, respectively, the FCR and SR were also decreased to 1.39 ± 0.04%/h and 2.26 ± 0.14 mg/kg/d, respectively. The values of j 1 j 2 did not significantly change during this work. These results indicate that (1) changes in serum T 4 concentrations directly correlate with the SR of pFN, (2) increase in the pFN concentration in hyperthyroid rabbits can be explained by greater increase in the SR than shortening of the half life of pFN, and (3) decrease in the pFN concentration in hypothyroid rabbits occurs by greater decrease in the SR than in prolongation of the half life of pFN.

Protein Degradation in Skeletal Muscle during Experimental Hyperthyroidism in Rats and the Effect of β-Blocking Agents*

beta-Blocking agents are increasingly used in the management of hyperthyroid patients. The effect of this treatment on increased muscle protein breakdown in the hyperthyroid state is not known. In the present study, experimental hyperthyroidism was induced in rats by daily ip injections of T3 (100 micrograms/100 g BW) during a 10-day period. Control animals received corresponding volumes of solvent. In groups of rats the selective beta-1-blocking agent metoprolol or the nonselective beta-blocker propranolol was infused by miniosmotic pumps implanted sc on the backs of the animals. Protein degradation was measured in incubated intact soleus and extensor digitorum longus muscles by determining tyrosine release into the incubation medium. The protein degradation rate in incubated extensor digitorum longus and soleus muscles was increased by 50-60% during T3 treatment. Metoprolol or propranolol did not influence muscle protein breakdown in either T3-treated or control animals. The results suggest that T3-induced increased muscle proteolysis is not mediated by beta-receptors, and muscle weakness and wasting in hyperthyroidism might not be affected by beta-blockers.

Effects of Beta-Blocking Agents on Urinary Excretion of 3-Methylhistidine during Experimental Hyperthyroidism in Rats

Beta-blocking agents are increasingly used as preoperative treatment of hyperthyroid patients. Relatively little is known about the effects of these drugs on metabolic alterations in hyperthyroidism. The aim of this investigation was to study the effects of two different beta-blocking agents on the urinary excretion of 3-methylhistidine (3-MH) during experimental hyperthyroidism in rats. Experimental hyperthyroidism was induced by daily intraperitoneal injections of triiodothyronine (T3; 100 micrograms/100 g body weight) for 3 days. Control animals were injected with corresponding volumes of solvent. Groups of rats received food enriched with metoprolol (8.8 mmol/kg of diet) or propranolol (3.3 mmol/kg of diet) or food without additions. Urinary 3-MH excretion was increased by about 40% during experimental hyperthyroidism. A similar increase of 3-MH excretion was found in animals receiving T3 + metoprolol, whereas the excretion of 3-MH was reduced to control level in hyperthyroid rats receiving propranolol. No effects of metoprolol or propranolol on 3-MH excretion were found in control animals. Although the source of 3-MH cannot be exactly defined, the present results indicate that increased proteolysis in skeletal muscle and/or other tissues during experimental hyperthyroidism was reduced by propranolol.

Experimental hyperthyroidism stimulates axonal growth in mesothelial chambers

An experimental model is presented for studying axonal growth after experimental hyperthyroidism and hypothyroidism. The left sciatic nerve of the rat was transected and transposed to the back. The proximal nerve stump was inserted into a 50-mm-long mesothelial chamber leaving the distal end of the chamber open. Different groups of young adult rats were given daily injections of thyroxine ( 10 μ g 100 g body weight) or the goitrogen, thiamazol, in the drinking water (0.125 g/liter) for 12 weeks. Thyroxine treatment increased significantly the extent of axonal outgrowth from the proximal nerve stump compared with untreated rats. Experimental hypothyroidism (thiamazol treatment), evidenced by a retarded body growth, did not affect the extent of axonal outgrowth. In other experiments the left proximal nerve stump was crossanastomosed with the right distal nerve stump. The two nerve stumps were bridged with a mesothelial chamber leaving a 15-mm gap. This gap distance is known from our previous studies to inhibit axonal overgrowth to the distal nerve stump. As evidenced by histological evaluation, in three of six thyroxine-treated rats, axons had bridged the 15-mm gap. We conclude that experimentally induced hyperthyroidism enhances axonal growth in mesothelial chambers.

Effects of isoproterenol on rubidium transport in slow- and fast-twitch muscles from euthyroid and hyperthyroid rats.

The influence of experimental hyperthyroidism on the catecholamine induced stimulation of rubidium ion transport in the soleus (SOL), a slow-twitch muscle and the extensor digitorum longus (EDL), a fast-twitch skeletal muscle of rats was studied. Thyroxine administration (800 micrograms/kg/day), for ten days induced a rise of ouabain-sensitive 86Rb uptake in SOL muscle, without affecting the ouabain-insensitive uptake, whereas both fractions of 86Rb uptake were increased in EDL muscle from hyperthyroid rats. Isoproterenol (5 mumol/l) caused a two-fold rise in ouabain-sensitive Rb uptake of euthyroid SOL muscle, while in hyperthyroid SOL it could stimulate only the ouabain-insensitive fraction of 86Rb influx. On the other hand, the stimulating action of isoproterenol on euthyroid EDL muscle was due to an enhancement of ouabain-insensitive Rb uptake, but in hyperthyroid EDL it failed to stimulate the ouabain-insensitive transport and caused a marked rise in ouabain-sensitive Rb uptake. The changes in catecholamine mediated transport properties in SOL muscle may be related to fibre type transformation induced by thyroid hormone, although in EDL the changes of catecholamine stimulation are unlikely due to fibre type conversion. Basal and isoproterenol stimulated cAMP levels were significantly reduced in both EDL and SOL muscles from hyperthyroid rats, in contrast with an insignificant decrease in net rubidium uptake caused by isoproterenol at the same concentration.

Modulatory effects of thyroxine treatment on central and peripheral benzodiazepine receptors in the rat.

The effects of 10 days of D-thyroxine (T4) treatment on central benzodiazepine (BZ) receptors in the brain and on peripheral-type BZ binding sites in the heart, kidney, and testis of rats were studied. The experimental hyperthyroidism resulted in an increase in the density of cortical central BZ receptors, without any alteration of the affinity of the receptors to [3H]flunitrazepam. The increase in cortical central BZ receptors was also accompanied by the up-regulation of peripheral BZ binding sites in the heart, kidney, and testis. The affinity of the peripheral BZ binding sites for the ligand [3H]PK 11195 was not affected by T4 treatment in any of these three organs. The increase in the density of brain cortical central BZ receptors was less prominent than the increase in the peripheral BZ binding sites. The modulatory effect of T4 treatment on central and peripheral BZ receptors might be attributed to the direct interaction of the thyroid hormone at these sites or might reflect a physiological compensatory adaptation mechanism to thyrotoxicosis associated with hypermetabolism, anxiety, and stress.