(1/3269) The epizootiology and pathogenesis of thyroid hyperplasia in coho salmon (Oncorhynchus kisutch) in Lake Ontario.
The thyroid glands of coho salmon collected at different stages of their anadromous migration exhibited progressive and extensive hyperplasia and hypertrophy. The incidence of overt nodule formation rose from 5% in fish collected in August to 24% in fish collected in October. The histological picture of the goiters was similar to that found in thiourea-treated teleosts and thiouracil-treated mammals. There was a concomitant, significant decrease in serum thyroxine and triiodothyronine values between September and October (thyroxine, 1.0+/-0.3 mug/100 ml and 0.4 mug/100 ml in September and October, respectively; triiodothyronine, 400.3+/-51.6 ng/100 ml and 80.2 ng/100 ml in September and October, respectively) and marked hypertrophy and hyperplasia of thyrotrophs. These data indicate a progressive hypothyroid condition which, although it may be linked to iodide deficiency, may well be enhanced by other environmental factors. The evidence for involvement of other factors is discussed. (+info)
(2/3269) Thyroid hormone promotes the phosphorylation of STAT3 and potentiates the action of epidermal growth factor in cultured cells.
We have examined the effects of l-thyroxine (T4) on the activation of signal transducer and activator of transcription 3 (STAT3) and on the STAT3-dependent induction of c-Fos expression by epidermal growth factor (EGF). T4, at a physiological concentration of 100 nM, caused tyrosine phosphorylation and nuclear translocation (i.e. activation) of STAT3 in HeLa cells in as little as 10-20 min. Activation by T4 of STAT3 was maximal at 30 min (15+/-4-fold enhancement; mean+/-S.E.M.) in 18 experiments. This effect was reproduced by T4-agarose (100 nM) and blocked by CGP 41251, genistein, PD 98059 and geldanamycin, inhibitors of protein kinase C (PKC), protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK) kinase and Raf-1 respectively. Tyrosine-phosphorylated MAPK also appeared in nuclear fractions within 10 min of treatment with T4. In the nuclear fraction of T4-treated cells, MAPK immunoprecipitate also contained STAT3. The actions of T4 were similar in HeLa and CV-1 cells, which lack thyroid hormone receptor (TR), and in TR-replete skin fibroblasts (BG-9). T4 also potentiated the EGF-induced nuclear translocation of activated STAT1alpha and STAT3 and enhanced the EGF-stimulated expression of c-Fos. Hormone potentiation of EGF-induced signal transduction and c-Fos expression was inhibited by CGP 41251, geldanamycin and PD 98059. Therefore the non-genomically induced activation by T4 of STAT3, and the potentiation of EGF by T4, require activities of PKC, PTK and an intact MAPK pathway. (+info)
(3/3269) Inhibition by lead of production and secretion of transthyretin in the choroid plexus: its relation to thyroxine transport at blood-CSF barrier.
Long-term, low-dose Pb exposure in rats is associated with a significant decrease in transthyretin (TTR) concentrations in the CSF. Since CSF TTR, a primary carrier of thyroxine in brain, is produced and secreted by the choroid plexus, in vitro studies were conducted to test whether Pb exposure interferes with TTR production and/or secretion by the choroid plexus, leading to an impaired thyroxine transport at the blood-CSF barrier. Newly synthesized TTR molecules in the cultured choroidal epithelial cells were pulse-labeled with [35S]methionine. [35S]TTR in the cell lysates and culture media was immunoprecipitated and separated by SDS-PAGE, and quantitated by autoradiography and liquid scintillation counting. Pb treatment did not significantly alter the protein concentrations in the culture, but inhibited the synthesis of total [35S]TTR (cells + media), particularly during the later chase phase. Two-way ANOVA of the chase phase revealed that Pb exposure (30 microM) significantly suppressed the rate of secretion of [35S]TTR compared to the controls (p < 0.05). Accordingly, Pb treatment caused a retention of [35S]TTR by the cells. In a two-chamber transport system with a monolayer of epithelial barrier, Pb exposure (30 microM) reduced the initial release rate constant (kr) of [125I]T4 from the cell monolayer to the culture media and impeded the transepithelial transport of [125I]T4 from the basal to apical side of epithelial cells by 27%. Taken together, these in vitro data suggest that sequestration of Pb in the choroid plexus hinders the production and secretion of TTR by this tissue. Consequently, this may alter the transport of thyroxine across this blood-CSF barrier. (+info)
(4/3269) Pseudogout attack associated with chronic thyroiditis and Sjogren's syndrome.
A 66-year-old woman, diagnosed with chronic thyroiditis at age 63, presented with anorexia and fatigue. Therapy for the chronic thyroiditis consisted of levothyroxine sodium (100 microg/day). Her symptoms were attributed to the insufficient supply of levothyroxine sodium. Following a dosage increase to 150 microg/day, she suffered from an acute attack of pseudogout. Clinical features were complicated by Sjogren's syndrome, which appeared after treatment onset. Pseudogout was effectively treated by colchicine after administration of diclofenac sodium failed to alleviate the symptoms. Pseudogout is a recognized complication of thyroid replacement therapy, but association with Sjogren's syndrome has not been previously reported. (+info)
(5/3269) Heart hypertrophy induced by levothyroxine aggravates ischemic lesions and reperfusion arrhythmias in rats.
AIM: To develop a cardiac hypertrophic model in rats. METHODS: Rats were i.p. levothyroxine 0.5 mg.kg-1.d-1 x 10 d. The action potentials of right papillary muscles were recorded by standard glass-microelectrode technique. The left coronary artery was ligated followed by reperfusion and the apparent infarcted zone (AIZ) was determined by tetracycline fluoresence, and the superoxide dismutase (SOD) activity and malondialdehyde (MDA) product in myocardium were also measured. RESULTS: In the rats treated by levothyroxine, the heart was hypertrophic and the action potential duration (APD) and effective refractory period (ERP) were prolonged, the APD20, APD50, APD90, and ERP were prolonged by 80%, 79%, 74%, and 68%, respectively. No changes in resting potential (RP), action potential amplitude (APA), and Vmax were produced. The incidence of heart arrest (8/8) and the risk of death (67 +/- 0) induced by ischemia-reperfusion in rats with hypertrophic heart was higher than those in normal rats (4/10 and 44 +/- 19, respectively). The AIZ was expanded markedly in hypertrophic heart, and attenuated by lidocaine and propranolol. CONCLUSION: Levothyroxine-induced heart hypertrophy is a suitable model for severe ischemia and arrhythmias in rats. (+info)
(6/3269) Histamine aggravated levothyroxine-induced cardiomyopathy in guinea pigs.
AIM: To study effects of histamine on cardiomyopathy. METHODS: Cardiomyopathy model was developed in guinea pig by i.p. levothyroxine 0.5 mg.kg-1.d-1 for 10 d. Langendroff's hearts were perfused. ECG and contractile force were recorded. Histamine (5 micrograms) was given by intra-aortic injection. Histamine content of coronary venous effluent was determined fluorometrically. RESULTS: Attack of histamine on cardiomyopathy was severer than that in normal hearts. Tachycardia was more prominent; atrioventricular conduction block occurred earlier; decrease in coronary flow was more marked. Uptakes of histamine were 37% in the model and 19% in the normal hearts (P < 0.01). CONCLUSION: Histamine aggravated levothyroxine-cardiomyopathy. (+info)
(7/3269) Hormonal changes in thalassaemia major.
Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed. (+info)
(8/3269) Developmental aspects of glutathione S-transferase B (ligandin) in rat liver.
The postnatal development in male Sprague-Dawley rats of hepatic glutathione S-transferase B (ligandin) in relation to the other glutathione S-transferases is described. The concentration of glutathione S-transferase B in 1-day-old male rats is about one-fifth of that in adult animals. The enzyme reaches adult concentrations 4-5 weeks later. When assessed by substrate specificity or immunologically, the proportion of transferase B relative to the other glutathione S-transferases is high during the first week after birth. At this age, 67.5% of the transferase activity towards 1-chloro-2,4-dinitrobenzene is immunoprecipitable by anti-(transferase B), compared with about 50% in adults and older pups. Between the second and the fifth postnatal week, the fraction of transferase B increases in parallel fashion with the other transferases in hepatic cytosol. Neither L-thyroxine nor cortisol induce a precocious increase in glutathione S-transferase activity. Phenobarbital did induce transferase activity towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene in both pups and adults. The extent of induction by phenobarbital was a function of basal activity during development such that the percentage stimulation remained constant from 5 days postnatally to adulthood. (+info)