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      Red Cell Sodium and Ionic Fluxes in Patients with Hyper- and Hypothyroidism

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          Abstract

          To investigate the status of the Na + concentrations [Na +]i, K + concentrations [K +]i and ionic fluxes in red cells of human subjects with abnormal thyroid function, we measured the Na +-K + pump activity as well as Na +-K + contransport (CoT), Na +-Li + countertransport (CTT) and Na + passive permeability in erythrocytes of 37 normal subjects, 19 untreated hyperthyroid patients, 12 treated hyperthyroid patients and 9 hypothyroid patients with T4 replacement.

          The mean [Na +]i value in the untreated hyperthyroidism group was significantly higher than that in the normal subjects (p<0.5), but not significantly different from that in the treated hyperthyroidism group. The mean [Na +]i value in the hypothyroidism with T4 replacement group, however, was significantly lower than that in the normal group (p<.01). We did not find any significant difference of [K +]i in comparing each group. It was found that the Na +-K + pump activity in erythrocytes was significantly increased in untreated hyperthyroidism (mean; 23.4% above control, p<10 −5), but there was no significant difference in treated hyperthyroidism and hypothyroid patients with T4 replacement. The rate constant for ouabain-sensitive Na + efflux in the hypothyroidism with T4 replacement group was markedly higher than that in normal subjects (p<.01), but not significantly different in the untreated hyperthyroidism group. We observed a significant increase of the Na + CoT value in the patients with untreated hyperthyroidism as campared with that of the normal subjects (p<.05), but there was no significant difference in the patients treated for hyperthyroidism and the hypothyroidism with T4 replacement group. However, the rate constant for Na +-CoT in the patients with hypothyroidism with T4 replacement was significantly higher than that in normal subjects (p<.05). We observed a marked decrease of Na +-Li +CTT value in the patients with untreated hyperthyroidism versus that in the normal group (p<.01). Passive Na + permeability in the patients with untreated hyperthyroidism was markedly increased (p<.05), and was markedly decreased in the patients with hypothyroidism with T4 replacement compared to normal subjects (p<.01). It can be concluded from these studies that an increase in Na +-K + pump activity in the patients untreated for hyperthyroidism might then be regarded as a secondary adaptive cellular response to higher [Na +]i values due to enhanced passive Na + permeability, rather than a direct effect of the thyroid hormone.

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          Most cited references30

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          Mechanism of thyroid calorigenesis: role of active sodium transport.

          The hypothesis that thyroid calorigenesis is mediated by stimulation of active Na(+) transport was tested by measuring the Q(o2) of liver slices and skeletal muscle (diaphragm) from thyroxine- and triiodothyronine-injected thyroidectomized and normal rats in media fortified with ouabain (10(-3) M) and/or free of Na(+) or K(+). In both tissues, more than 90% of the increase in Q(o2) produced by injections of thyroid hormone in euthyroid rats was derived from increased energy utilization by the Na(+) pump. In triiodothyronine-treated thyroidectomized rats, activation of Na(+) transport accounted for 90% or more of the increment in Q(o2) in liver and 40% or more of the increment in diaphragm. Intracellular Na(+), K(+), and Cl(-) concentrations were measured in euthyroid and hyperthyroid liver and diaphragm. The transmembrane Na(+) and K(+) concentration differences were significantly increased in both tissues by the administration of triiodothyronine. These results indicate that thyroid hormone activates Na(+) extrusion and K(+) accumulation either by increasing the local concentration of ATP or by direct stimulation of the Na(+) pump.
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            The Mechanism of the Calorigenic Action of Thyroid Hormone

            In an earlier study, we proposed that thyroid hormone stimulation of energy utilization by the Na+ pump mediates the calorigenic response. In this study, the effects of triiodothyronine (T3) on total oxygen consumption (Q OO2 ), the ouabain-sensitive oxygen consumption [Q OO2 (t)], and NaK-ATPase in liver, kidney, and cerebrum were measured. In liver, ∼90% of the increase in Q OO2 produced by T3 in either thyroidectomized or euthyroid rats was attributable to the increase in Q OO2 (t). In kidney, the increase in Q OO2 (t) accounted for 29% of the increase in Q OO2 in thyroidectomized and 46% of the increase in Q OO2 in euthyroid rats. There was no demonstrable effect of T3 in euthyroid rats on Q OO2 or Q OO2 (t) of cerebral slices. The effects of T3 on NaK-ATPase activity in homogenates were as follows: In liver +81% from euthyroid rats and +54% from hypothyroid rats. In kidney, +21% from euthyroid rats and +69% from hypothyroid rats. T3 in euthyroid rats produced no significant changes in NaK-ATPase or Mg-ATPase activity of cerebral homogenates. Liver plasma membrane fractions showed a 69% increase in NaK-ATPase and no significant changes in either Mg-ATPase or 5'-nucleotidase activities after T3 injection. These results indicate that thyroid hormones stimulate NaK-ATPase activity differentially. This effect may account, at least in part, for the calorigenic effects of these hormones.
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              Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle.

              The effect of thyroid status on QO2, QO2 (t) and NaK-ATPase activity was examined in rat skeletal muscle. QO2(t) (i.e. Na+-transport-dependent respiration) was estimated with ouabain or Na+-free media supplemented with K+. In contrast to the effects of ouabain on ion composition, intracellular K+ was maintained at about 125 meq/liter, and intracellular Na+ was almost nil in the Na+-free media. The estimates of QO2(t) were independent of the considerable differences in tissue ion concentrations. The increase in QO2(t) account for 47% of the increase in QO2 in the transition from the hypothyroid to the euthyroid state and 84% of the increase in the transition from the euthyroid to the hyperthyroid state. Surgical thyroidectomy lowered NaK-ATPase activity of the microsomal fraction (expressed per milligram protein) 32%; injections of triodothyronine (T3) increased this activity 75% in initially hypothyroid rats and 26% in initially euthyroid rats. Thyroidectomy was attended by significant falls in serum Ca and Pi concentrations. Administration of T3 resulted in further declines in serum Ca and marked increases in serum Ps concentrations. Similar effects were seen in 131I-treated rats, but the magnitude of the declines in serum Ca were less. The effects of T3 on QO2, QO2(t), and NaK-ATPase activity of skeletal muscle were indistinguishable in the 131I-ablated and surgically thyroidectomized rats. In thyroidectomized or euthyroid rats given repeated doses of T3, QO2(t) and NaA-ATPase activity increased proportionately. In thyroidectomized rats injected with single doses of T3, either 10, 50, or 250 mug/100 g body wt, QO2(t) increased linearly with NaK-ATPase activity. The kinetics of the NaK-ATPase activity was assessed with an ATP-generating system. T3 elicited a significant increase in Vmax with no change in Km for ATP.
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                Author and article information

                Journal
                Korean J Intern Med
                Korean J. Intern. Med
                The Korean Journal of Internal Medicine
                Korean Association of Internal Medicine
                1226-3303
                2005-6648
                January 1989
                : 4
                : 1
                : 18-27
                Affiliations
                Department of Internal Medicine, Catholic University Medical College, Seoul, Korea
                Green Cross Bioscience Reference Laboratory
                Author notes
                Address reprint requests: Young-Suk Yoon, M.D., Department of Internal Medicine, Catholic University, Medical College, 505 Banpodong Seocho-ku, Seoul, Korea
                Article
                kjim-4-1-18-3
                10.3904/kjim.1989.4.1.18
                4534973
                2484839
                05d80ed0-6ff8-4ab0-a6e7-eb5d11bf6cb1
                Copyright © 1989 The Korean Association of Internal Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Original Article

                Internal medicine
                hyperthyroidism,intracellular sodium,na+-k+ pump activity,na+-k+ cotransport,na+-li+ counter-transport,passive na+ permeability

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