The Influence of β-Adrenoceptor Blocking Agents on Plasma Thyroxine and Triiodothyronine

Wiersinga, Wilmar M.; Touber, J. L.

doi:10.1210/jcem-45-2-293

Cited by 111 publications

(34 citation statements)

References 29 publications

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“…propylthiouracil (23,24), glucocorticoids in high doses (25)(26)(27), certain radiographic contrast media (28,29), and the beta adrenergic blocking agents, propranolol (30) and amiodarone (31). It has generally been assumed that all of these factors act primarily to decrease production of T3 from T4, rather than to increase peripheral degradation ofT3, and direct studies have shown this to be true in the case of cirrhosis (5,22), fasting (12,32), and diabetes (15).…”

mentioning

confidence: 99%

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Balsam¹,

Ingbar²

1979

J. Clin. Invest.

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A B S T R A C T Studies were performed to explore the mechanism underlying the impaired generation of 125-I-3,5,3'-triiodothyronine (T3) from 1251-thyroxine (T4) (T3-neogenesis) in preparations of liver from rats fasted for 48 h and the prevention of this effect by the feeding of glucose. T3-neogenesis in livers from fasted animals and those fed chow or glucose was assessed in various mixtures of crude microsomal fractions with either buffer or cytosols. T3-neogenesis was mediated by an enzyme present in the microsomal fraction whose activity was enhanced by cytosolic cofactor(s). In livers from animals fasted for 48 h, the supporting activity of cytosol was decreased, whereas the activity of the enzyme was unaffected. Administration of glucose as the sole nutritional source prevented the decrease in the supporting activity of hepatic cytosol that was regularly observed in the case of animals totally deprived of food.The diminished supporting activity for T3-neogenesis provided by liver cytosol from fasted animals was restored to normal by enrichment with either NADPH or GSH, but the two cofactors appeared to act at different loci. GSH stimulated T3-neogenesis in microsomes incubated in the absence of cytosol, i.e., in buffer, whereas NADPH did not. The stimulatory effect of both agents was blocked by the sulfhydryl oxidant, diamide, which also inhibited T3-neogenesis in mixtures of microsomes with cytosols. Taken together, these observations suggest that GSH acts directly on the enzyme in the crude microsomal fraction, whereas NADPH acts within the cytosol, possibly by increasing the concentration of GSH through the action of the enzyme glutathione reductase, for which NADPH is a cofactor. In this light, the decreased supporting activity of hepatic cytosol

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confidence: 99%

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Balsam¹,

Ingbar²

1979

J. Clin. Invest.

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“…As judged from concentrations of T3 and rT3 in serum, such shifts do indeed occur. A diversity of conditions has been shown to be associated with decreases in serum T3 concentration, among them starvation (3-6), acute or severe chronic illness (7,8), operative stress (9,10), anorexia nervosa (11)(12)(13), and the administration ofglucocorticoids (14)(15)(16), the adrenergic blocking agents amiodarone (17), or propranolol (18), or propylthiouracil (PTU) (19,20). In many ofthese situations there occurs an accompanying increase in serum rT3 concentration (4,6,8,15,17 tissues obtained from Sprague-Dawley rats of the CD strain (Charles River Breeding Laboratories, Wilmington, Mass.).…”

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confidence: 99%

“…10 or 20 ,ul of extract was rapidly evaporated under nitrogen, the T3 was solubilized in rat serum freed of T3 by charcoal adsorption, and the T3 content was assayed. Preliminary studies indicated that [10][11][12][13][14][15][16][17][18][19][20] j1 of tissue extract incubated without substrate T4 could be introduced into the radioimmunoassay without influencing the configuration ofthe standard curve. Negligible generation ofT3 from T4 was detected in simultaneously incubated tissuefree blanks.…”

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confidence: 99%

The Influence of Fasting, Diabetes, and Several Pharmacological Agents on the Pathways of Thyroxine Metabolism in Rat Liver

Balsam¹,

Ingbar²,

Sexton³

1978

J. Clin. Invest.

173

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A B S T R A C T As judged from both paper and column chromatography, slices or homogenates of liver from rats fasted for 48 h displayed a lesser rate of generation of 1251-labeled 3,5,3'-triiodothyronine (T3) from 1251-labeled thyroxine (T4) added to incubation media than did preparations from normal chow-fed animals. A similar defect in the conversion of T4 to T3 in the livers of fasted animals was observed when preparations were incubated with substrate concentrations of T4 so that T3 generation could be assessed by radioimmunoassay. The effect offasting could be prevented, wholly or in part, by administration of glucose in the drinking water to otherwise fasted animals, and the degree ofprevention appeared to be proportional to the concentration of glucose employed. Diminished generation of T3 from T4 was similarly evident in the livers of animals with streptozotocin-induced diabetes mellitus, and this defect was overcome by the provision of insulin in vivo, but not in vitro. Decreased formation of T3 from T4 was also observed in preparations of liver from animals given dexamethasone, amiodarone, and propylthiouracil. In no case could these effects on the net formation of T3 from T4 be explained by effects of the experimental conditions on the degradation of the T3 generated, as judged from the rate of degradation of exogenous 125I-T3 measured in parallel incubates.An analysis of the rate of disappearance of 125I-T4 from reaction mixtures in relation to the rate of appearance of 125I-T3 and 1251-iodide was employed to estimate the activity of the 5-monodeiodinating pathway of T4 metabolism that leads to the formation of 3,3',5'-triiodothyronine (reverse T3). Such estimates indicated that reverse T3 formation was actively proceeding in the preparations studied, was slightly enhanced by Received for publication 9 November 1977 and in revised form 14 March 1978. fasting, was unaffected by dexamethasone and amiodarone, and was markedly inhibited by propylthiouracil.In view ofthe similarities between the effect ofthese experimental manipulations on the generation of T3 from T4 by rat liver in vitro to their effects on the production rates and serum concentrations of T3 in man, it is concluded that the rat liver system provides a suitable model for the study of factors that influence the conversion of T4 to T3 in man. In addition, the findings strongly indicate that this process, at least in the liver, is closely linked to the utilization of carbohydrate. INTRODUCTION Recent studies have provided convincing evidence that 3,5,3'-triiodothyronine (T3)l contributes a major portion to the overall metabolic action of the thyroid hormones within the peripheral tissues. It is evident, moreover, that much of the T3 found in the blood of normal man arises, not by direct secretion from the thyroid gland, but rather from the peripheral monodeiodination of thyroxine (T4) in its outer ring at the 5'-position. It is generally agreed that this reaction results in activation of the hormone molecule, as T3 is several times more ...

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“…Los betabloqueadores adrenérgicos, como el propanolol, cuyo empleo se ha hecho frecuente en los últimos años, resultan beneficiosos en el control de las manifestaciones cardiovasculares, particularmente de la taquicardia, pero su efecto es casi exclusivamente a través del bloqueo del sistema adrenérgico y sólo inhiben débilmente la conversión periférica de T4 a T3 en dosis altas (37,38), las que a su vez pueden deprimir la fibra miocárdica y desencadenar o empeorar una insuficiencia cardíaca (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

Section: Discussionunclassified

Empleo del Yopodato Sódico (Biloptin) en el tratamiento agudo de las complicaciones cardiovasculares severas del hipertiroidismo.

Seclén¹,

Pretell²,

Velasco-Tapia³

et al. 2014

Rev Med Hered

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The Influence of β-Adrenoceptor Blocking Agents on Plasma Thyroxine and Triiodothyronine

Cited by 111 publications

References 29 publications

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

The Influence of Fasting, Diabetes, and Several Pharmacological Agents on the Pathways of Thyroxine Metabolism in Rat Liver

Empleo del Yopodato Sódico (Biloptin) en el tratamiento agudo de las complicaciones cardiovasculares severas del hipertiroidismo.

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