Effect Of Thyroid Status Research Articles

Effect of thyroid status on ouabain binding to the human lymphocyte.

Lymphocyte Na-K ATPase was evaluated as an index of thyroid status in man. Lymphocytes from 24 untreated hypothyroid patients and 11 hyperthyroid subjects were sampled in parallel with normal lymphocytes, and Na-K ATPase activity was assessed by measurements of ouabain binding to a plasma membrane fraction or to whole cells. In both systems, ouabain bound saturably and specifically, resulting in linear Scatchard plots. Normal lymphocyte plasma membranes bound 2.30 +/- 0.16 pmol ouabain/mg protein (mean +/- SEM; n = 11), with a Kd of 68 +/- 12 nM. Intact normal lymphocytes bound 3.24 +/- 0.30 pmol ouabain/10(7) cells (n = 14), representing 189,000 sites/cell. In hypothyroidism, ouabain binding, when compared with normal cells sampled on the same day, was reduced by 22.0 +/- 5.3% (n = 11; P less than 0.001) in plasma membranes and by 29.1 +/- 3.5% (n = 14) in whole lymphocytes (P less than 0.001), but there was no significant change in the Kd in the membrane fraction. In 6 subjects, the decrease in ouabain binding to lymphocytes was reversed by thyroid hormone replacement. Red cells from hypothyroid subjects showed normal ouabain binding. Ouabain binding to hyperthyroid plasma membranes (2.42 +/- 0.18 pmol/mg protein) was not significantly different from normal. The results in hypothyroid subjects are consistent with the hypothesis that lymphocyte Na-K ATPase is regulated by thyroid hormones. However, lymphocyte Na-K ATPase does not increase in parallel with elevated thyroid hormone levels in hyperthyroidism. The mechanisms underlying these observations remain to be clarified.

Modulation by thyroid status of the actions of glucagon and dibutyryl adenosine 3',5'-monophosphate on metabolism of free fatty acids by the isolated perfused rat liver.

The interactions among effects of thyroid status, glucagon, and dibutyryl cAMP (DBcAMP) on the regulation of hepatic metabolism of FFA were studied in perfused livers isolated from euthyroid, hypothyroid, and hyperthyroid male rats. The animals were made hypothyroid by treatment with propylthiouracil or hyperthyroid by treatment with T3. Uptake of oleic acid by perfused livers was not altered by treatment of the animal with T3 or propylthiouracil, or by addition to the medium of glucagon (10-9 M), DBCAMP (2 × 10-5 M), or methylisobutylxanthine (MIX; 2 HIM). In agreement with previous data, hepatic formation and secretion of triglyceride were diminished and ketogenesis was stimulated by hyperthyroidism, glucagon, and DBcAMP. These effects of diminished triglyceride output and enhanced ketogenesis observed in hyperthyroidism were exacerbated by glucagon, while livers from hypothyroid rats were insensitive to the effects of glucagon. MIX, a phosphodiesterase inhibitor, reversed the insensitivity of the liver...

Effects of thyroid status on the structure of the very low density lipoprotein secreted by the perfused liver.

To determine whether hyperthyroidism or hypothyroidism affected the structure of the very low density lipoprotein (VLDL) secreted by the perfused rat liver, rats were pretreated with 0.9% NaCl, T3, or propylthiouracil. The livers were perfused with 0-332 mumol bovine serum albumin-oleate/h for 4 h. The structure of the secreted VLDL was determined by compositional analysis and the use of the fluorescence probe molecules diphenylhexatriene, trans-parinaric acid, and cis-parinaric acid. Compositional analysis indicated that the VLDL secreted by livers from rats pretreated with T3 had lower unsaturated to saturated fatty acid ratios than did controls, regardless of the amount of oleate infused. Fluorescence polarization of diphenylhexatriene indicated that the interior core lipids of VLDL secreted by livers from T3-treated rats were more rigid than those secreted by livers of euthyroid animals. Arrhenius plots of polarization and corrected fluorescence of diphenylhexatriene and trans-parinaric acid, but not cis-parinaric acid, revealed that characteristic temperatures were shifted 8 to 10 C higher in VLDL secreted by livers from rats pretreated with T3. Treatment of rats for 7 days with propylthiouracil under these mild conditions did not alter the structure or composition of the VLDL secreted by the perfused liver. In summary, the lipid changes in the VLDL secreted by perfused rat livers from hyperthyroid animals were consistent with these VLDL being more rigid particles than those secreted by livers from euthyroid rats, independent of the infusion rate of the FFA.

Modulation by thyroid status of hepatic low Km phosphodiesterase.

The effects of thyroid status on the activity of hepatic cAMP phosphodiesterase (PDE) were studied in the rat. Male rats were rendered hyperthyroid by treatment with T3 or hypothyroid by treatment with propylthiouracil. The hepatic particulate low Km PDE was solubilized, and its activity was measured at concentrations of 0.12-1.3 microM cAMP. The Km decreased in hypothyroidism and tended to increase in hyperthyroidism with respect to individual controls. The maximal velocity (Vmax) was unaffected by changes in thyroid status. The increases in Km correlated with increasing plasma T3, whereas the Vmax did not. Concentrations of cAMP increased in the livers from hyperthyroid rats and decreased in those from hypothyroid, in comparison with euthyroid rat livers. The effects of thyroid status on various aspects of hepatic lipid metabolism reported from this laboratory may, in part, have resulted from alterations in hepatic cAMP concentrations. These alterations, may have resulted secondarily from changes in the activity of hepatic PDE by changes in the Km for cAMP with little change in the Vmax.

Effect of thyroid status on α- and β-catecholamine responsiveness of hamster adipocytes

It has been suggested that part of the increased β-catecholamine responsiveness in hyperthyroid animals is due to a decrease in α-catecholamine action. The present results indicate that neither hyperthyroidism nor hypothyroidism altered the α 2-adrenergic inhibition of adenylate cyclase or the α 1-adrenergic stimulation of phosphatidylinositol turnover in adipocytes from the white adipose tissue of hamster. No effect of hyperthyroidism was found on the K d of [ 3H]dihydroegocryptine or the number of binding sites in membranes prepared from hamster adipocyte tissue. The stimulation of cyclic AMP due to β-catecholamines was enhanced in adipocytes from hyperthyroid hamster, as was lipolysis. However, in adipocytes from hyperthyroid hamster the maximal stimulation of cyclic AMP due to isoproterenol, ACTH or epinephrine plus yohimbine, as seen in the presence of adenosine deaminase and theophylline, was less than in adipocytes from euthyroid hamsters. The activation of adenylate cyclase by isoproterenol was the same in membranes from hyperthyroid as compared to those from euthyroid hamsters in the absence or presence of guanine nucleotides. These data suggest that thyroid status has little effect on α-catecholamine action but enhances the activation of lipolysis by β-catecholamine agonists.

The effects of thyroid status on some properties of rat fast-twitch muscle.

The effects of different thyroid states on some histochemical and biochemical properties of fast-twitch muscle were studied using rat extensor digitorum longus (EDL) muscle. This muscle was found to be much less responsive to thyroidal influence than the slow-twitch soleus muscle. In EDL muscles of hypothyroid rats, fast leads to slow conversions were observed in fibre type composition, myosin ATPase activity and light chain pattern, and in the subunit composition of lactate dehydrogenase, while the only significant slow leads to fast conversion observed in thyrotoxicosis was a decrease in the proportion of slow-oxidative fibres. Denervation of the hypothyroid muscle produced the highest degree of fast leads to slow transformation. These findings support the view that denervation and dysthyreosis alter gene expression in muscle by independent mechanisms.

Effect of thyroid status on beta-adrenoreceptors and muscarinic receptors in the rat lung.

1. The effects of thyroid status on the specific binding of the muscarinic ligand (-)-[3H]quinuclidinyl benzilate (QNB) and of the beta-adrenoreceptor ligand (-)-[3H]dihydroalprenolol (DHA) in the adult rat lung were investigated. 2. The specific binding of (-)-[3H]quinuclidinyl benzilate (QNB) to lung membranes was saturable and the equilibrium dissociation constant (KD) determined from Scatchard analysis was 54 pM. Kinetic analysis of the binding of [3H]QNB yielded a KD of 42 pM. [3H]QNB binding was inhibited by muscarinic agonists and antagonists, the order of their potency was l-hyoscyamine greater than atropine greater than scopolamine greater than oxotremorine greater than carbachol. These data were consistent with [3H]QNB binding to the muscarine receptor. 3. Adult male rats treated for 2 weeks with the antithyroid agent 3-amino-1,2,4-triazole (ATZ) showed a 52% and 80% reduction in the serum concentration of triiodothyronine (T3) and thyroxine (T4) respectively. These hypothyroid rats also had a 39% decrease in the concentration of lung beta-adrenoreceptors and a 37% decrease in the concentration of lung muscarinic receptors as compared to euthyroid controls. Concurrent treatment of rats with ATZ and T4 for 2 weeks resulted in a reduction of 15% and 20% in the concentration of lung beta-adrenoreceptors and muscarinic receptors respectively. The KD values for [3H]DHA and [3H]QNB binding did not change with the ATZ or ATZ+T4 treated groups. 4. Administration of T4 (500 micrograms/kg/day) to male rats for 12 days did not result in any significant change in the concentration of either beta-adrenoreceptors or muscarinic receptors compared to euthyroid controls. No change in the KD values for [3H]DHA or [3H]QNB binding were detected. 5. The results show that hypothyroid rats have a reduced lung concentration of both beta-adrenoreceptors and muscarinic receptors whereas in hyperthyroid rats these receptors do not significantly change from euthyroid controls.

Interaction of thyroid status and diet on muscle protein breakdown in the rat, as measured by N τ-methylhistidine excretion

The effects of thyroid status and of dietary protein and energy content on muscle protein breakdown have been compared in young rats, using urinary N τ-methylhistidine (3-methylhistidine; 3-Mehis) output as a measure of myofibrillar protein breakdown. Recently thyroidectomized young rats receiving an adequate diet grew slowly and showed a reduction in 3-Mehis output, relative to the weight of their leg muscles. When the thyroidectomized rats were given 2–5 μg thyroxine (T 4) per 100 g body weight, output of 3-Mehis increased, even when growth was prevented by feeding a diet low in protein. This demonstrates that thyroid-status affects muscle protein breakdown through a mechanism other than via a change in growth rate. In confirmation of previous studies, administration of a diet low in protein to young rats prevented growth and reduced output of 3-Mehis relative to leg muscle weight. The reduction in protein breakdown is not likely to be due to reduced thyroid function, since the diet low in protein increased plasma total triiodothyronine (T 3) levels. Furthermore, thyroidectomized rats fed the low-protein diet also underwent a decrease in output of 3-Mehis. In contrast to protein deficiency, a moderate dietary energy deficiency allowed some growth to occur, and output of 3-Mehis, relative to muscle mass, was not depressed. Nevertheless, total T 3 concentration in the plasma of these animals was considerably reduced, indicating once more that total circulating thyroid hormone levels are not the only determinants of muscle protein breakdown. Finally, reduced plasma total T 3 levels occurred in energy-deficient diets even in thyroidectomized rats receiving exogenous T 4. This suggests that diet affects metabolism of the hormone independently of changes in secretory output from the thyroid gland.

Effects of thyroid states on the Cori cycle, glucose-alanine cycle, and futile cycling of glucose metabolism in rats

The effect of thyroid status on glucose recycling was measured in intact rats by comparing the fates of differently labeled [ 3H]- and [ 14C]glucose. Glucose recycling at the level of three-carbon compounds (i.e., Cori and glucose-alanine cycles) was measured by comparing the rates of turnover of [6- 3H]- and [6- 14C]glucose in the same animal. The rate of recycling increased (33–110%) in hyperthyroid rats and decreased (22–30%) in hypothyroid (thyroidectomized) rats. The relative importance of the Cori and glucose-alanine cycles was measured by analyzing the labeled glycolytic intermediates after the injection of labeled glucose; and by measuring the rate of glucose production from the infused labeled lactate and alanine. The results showed that the rate of the Cori cycle is much greater than the glucose-alanine cycle in rats. Substrate cycling at the level of glucokinase-glucose-6-phosphatase was measured by comparing the rates of turnover of [2- 3H]- and [6- 3H]glucose; and phosphofructokinase-fructose bisphosphatase was measured by comparing the rates of turnover of [3- 3H]- and [6- 3H]glucose. These cycles were also affected by thyroid states of the animals. The rate of the phosphofructokinase-fructose bisphosphatase cycle increased threefold in hyperthyroid rats and decreased by about half in hypothyroid rats. The glucokinase-glucose-6-phosphatase substrate cycle occurred at the rate of nearly 2 μmol/min/100 g body wt in the hyperthyroid, fasted rats; it was not detectable in hypo- or euthyroid rats. The contribution of the energy released by these cycles to thyroid thermogenesis was discussed. Effects of thyroid states on glucose metabolism in perfused muscles were also studied. There is an apparent shift in the source of energy for oxidation in the hyperthyroid rat. The ratio of lactate production to glucose uptake was significantly elevated in the hyperthyroid rats. This change predisposes for increased glucose recycling in hyperthyroid rats to avoid lactate accumulation and acidosis.

The effect of exercise, thyroid status and insulin-induced hypoglycaemia on the Achilles tendon reflex time in man.

The effect of moderate exercise on the Achilles tendon reflex half-relaxation time (ART) was observed in 28 hypothyroid, 35 euthyroid, and 20 hyperthyroid subjects of comparable age and sex. Both the resting ART and the decrease after exercise (delta ART) were longer in hypothyroid patients and shorter in hyperthyroid patients as compared to the euthyroid group. delta ART was strongly related to the resting ART rather than to the free thyroxine index. In four hypothyroid subjects, the half-time of recovery of the ART after exercise was similar, approx. 24 min. Insulin-hypoglycaemia in eight resting endocrine patients also caused a fall in ART similar to the post-exercise delta ART in the same patients. A possible catecholamine effect is indicated by the smaller post-exercise delta ART in nine hypertensive patients receiving chronic propranolol treatment, 320 mg daily, than that of a control group matched for age, sex, and resting ART. These studies suggest that submaximal exercise largely removes the differential effect of thyroid status on skeletal muscle contractility as measured indirectly by the ART. The effects of exercise and induced insulin-hypoglycaemia on delta ART may be mediated in part by endogenous catecholamines.

Effects of thyroid state on brain development: β-Adrenergic receptors and 5′-nucleotidase activity

The effect of thyroid status on β-adrenergic receptor binding and 5′-nucleotidase activity was studied in the forebrain and the cerebellum of the rat during the first 5 postnatal weeks. The developmental increase in β-adrenergic receptor binding was significantly depressed in thyroid deficiency in both the forebrain and the cerebellum. The effect was more pronounced in the cerebellum, where at day 35 the concentration and the total number of β-adrenergic receptor sites were reduced by 35% and 50% respectively. In contrast, hyperthyroidism had no significant effect on the development of β-adrenergic receptors in the brain. On the other hand, hyperthyroidism led to a sustained increase in the forebrain in the activity of 5′-nucleotidase, an enzyme which is also associated with plasma membranes and has been proposed to play some role in neurotransmission. In thyroid deficiency the enzyme activity was markedly depressed. The effect was significant from day 12 in the cerebellum and from day 21 in the forebrain, the maximal depression, at day 21, being 55% and 45% respectively. In comparison with these plasma membrane markers, the accretion of membranous proteins was less affected: although this was retarded in hypothyroidism and advanced in hyperthyroidism there was no residual effect at 35 days except those attributable to changes in organ size. The results indicated, therefore, that the biochemical specialization of cells, as reflected in certain plasma membrane constituents, are characteristically influenced in the developing brain by thyroid disorders.

Effect of thyroid status on insulin action in rat adipocytes and skeletal muscle.

Isolated adipocytes and soleus muscles prepared from mature rats, rendered hypothyroid by a low iodine diet and propylthiouracil, markedly resisted the ability of insulin to increase glucose utilization. In adipocytes, the sum of basal d-(1-(14)C)-glucose conversion to CO(2), glyceride-glycerol, and fatty acid was unaltered by hypothyroidism, although conversion to fatty acid was decreased. The response of each of these metabolic pathways to insulin at all concentrations tested was greatly diminished in hypothyroid rat adipocytes. 3-O-Methylglucose transport rates in the presence of insulin were not significantly different in adipocytes from hypothyroid as compared with euthyroid rats, although basal transport rates were significantly higher in the hypothyroid state. Lipolysis and cyclic AMP accumulation in adipocytes from hypothyroid rats in response to theophylline were markedly diminished compared with euthyroid controls, but insulin was about as effective in inhibiting lipolysis in these cells as in those derived from euthyroid animals. The binding of (125)I-insulin to adipocytes at several hormone concentrations was also shown to be unaffected by hypothyroidism. In soleus muscle, basal glucose conversion to H(2)O and glycogen was unaltered in the hypothyroid state, whereas insulin action on these pathways was markedly inhibited. The decrease in muscle insulin responsiveness was less marked than that observed in adipocytes. Uptake of either 2-deoxyglucose or l-arabinose in the presence or absence of insulin was similar in soleus muscles derived from euthryoid vs. hypothyroid rats. Similarly, insulin action on the conversion of soleus muscle glycogen synthase D to the I form in the absence of glucose was unaltered by hypothyroidism. We conclude that (a) hypothyroidism in mature rats leads to a marked decrease in the responsiveness of glucose metabolism in adipocytes and skeletal muscle to insulin; (b) no detectable impairment of the membrane insulin effector systems that mediate the regulation of adipocyte hexose transport and glycogen synthase is caused by hypothyroidism in this animal model; and (c) the cellular defect that leads to apparent insulin resistance of adipocyte and soleus muscle glucose utilization resides at the level of one or more intracellular enzymes involved in glucose catabolism.

Effects of thyroid status and choice of USP preparation on the pharmacokinetics of propylthiouracil in the beagle dog.

In vitro dissolution profile testing of 12 generic 6-propyl-2-thiouracil (PTU) formulations indicated significant differences in their solubilities in water and in 0.1N hydrochloric acid. Two products, representing the extremes of solubility, were subsequently tested for bioavailability. Bioavailability data from euthyroid, hyperthyroid, and hypothyroid beagle dogs indicated that the rate of PTU absorption varied appreciably between the two generic products studied. These results were consistent with the in vitro dissolution data. Comparisons of the pharmacokinetic parameters obtained for the euthyroid beagle dog to those reported for euthyroid man12 indicated that the beagle dog is an adequate model for PTU disposition in man. These combined results suggest that all generic formulations of PTU are not the same and that the most soluble product may be desirable in situations where rapid absorption is important, such as thyroid storm.

Alpha-adrenergic receptor in rat heart. Effects of thyroidectomy

The effects of thyroid status on alpha-adrenergic receptors in the rat myocardium were investigated. The potent antagonist [3H]dihydroergokryptine was used to identify alpha-adrenergic receptors in rat heart particulate and sarcolemmal fractions. Administration of triiodothyronine to thyroidectomized rats decreased specific binding to alpha-adrenergic receptors in heart particulate and sarcolemmal fractions by 41% and 45%, respectively. Scatchard analysis revealed that the cardiac sarcolemmal fraction from thyroidectomized rats contained 29.3 fmol/mg of protein, as compared with 17.0 fmol/mg of protein found in the heart preparation of thyroidectomized rats treated with triiodothyronine. The equilibrium dissociation constants for the interaction of receptors with dihydroergokryptine were similar (about 1.5 nM) in the heart sarcolemmal fractions derived from these two groups of rats. The results of this study demonstrate that thyroid hormone can regulate the number of cardiac alpha-adrenergic receptors. In addition, there appears to be a reciprocal relationship between alpha-adrenergic and beta-adrenergic receptors in the rat myocardium.

Effects of thyroid status on plasma adrenaline and noradrenaline concentrations in sheep during acute and chronic cold exposure.

In the first of two experiments, plasma concentrations of adrenaline (A), noradrenaline (NA), and glucose were determined in intact sheep and in surgically thyroidectomized sheep treated intramuscularly with either 0.125 or 0.25 mg triiodothyronine (T3) per day. On day 28 of exposure to temperatures of 22–25 or 2–5 °C, overall mean plasma concentrations of A were 0.07 and 0.15 ng/ml, respectively, and of NA were 0.30 and 0.45 ng/ml, respectively. Plasma A concentrations were higher in intact compared with thyroidectomized sheep on T3 therapy. Plasma glucose concentrations were increased by exposure to 2–5 °C and by T3 treatment. In a second experiment thyroidectomized sheep were kept at 22–26 °C and were either T3 treated (0.07 mg T3/day, im) or untreated. After 3 weeks, mean concentrations in the untreated sheep before acute cold and during the last hour of cold exposure (−23 °C) were, respectively: for A, 0.09 and 0.47 ng/ml; for NA, 0.46 and 3.15 ng/ml; and for glucose, 62.1 and 122.1 mg/100 ml. In T3-treated sheep the mean concentrations before and during cold were, respectively: for A, 0.07 and 0.22 ng/ml; for NA, 0.30 and 1.71 ng/ml; and for glucose, 59.6 and 82.3 mg/100 ml. The untreated sheep showed greater increases in plasma concentrations of A, NA, and glucose and in hematocrit values than T3-treated sheep, but had slightly smaller increases in metabolic rate, greater decreases in rectal temperature, and similar heart rates during cold exposure.

Effects of thyroid status and acute and chronic cold exposure on plasma catecholamine concentrations in sheep

Effects of thyroid status and acute and chronic cold exposure on plasma catecholamine concentrations in sheep

Muscarinic cholinergic receptors in rat heart. Effects of thyroidectomy.

The effects of thyroid status on muscarinic cholinergic receptors in the rat myocardium were investigated. The potent muscarinic antagonist [3H]quinuclidinyl benzilate was used to identify muscarinic cholinergic receptors in rat heart particulate fractions from control, hypothyroid, and hyperthyroid rats. Thyroidectomy increased specific [3H]quinuclidinyl benzilate binding to heart particulate fractions by about 60% as compared to euthyroid rat cardiac preparations. Administration of triiodothyronine to euthyroid rats decreased specific binding to muscarinic cholinergic receptors by about 20%. Scatchard analysis revealed that the cardiac particulate fraction from thyroidectomized rats contained 134 fmol of [3H]quinuclidinyl benzilate binding sites per mg of protein, as compared with 85 fmol/mg of protein found in the heart preparation of thyroidectomized rats chrinically treated with triiodothyronine. The equilibrium dissociation constant for the interaction of receptors with quinuclidinyl benzilate was the same (1 nM) in the heart particulate fractions derived from these two groups of rats. The results of this study demonstrate that thyroid hormone can regulate the number of cardiac muscarinic cholinergic receptors. Thus, the parasympathetic nervous system may participate in the cardiovascular abnormalities in different thyroid states.

THE RELATIONSHIP BETWEEN THYROID FUNCTION AND THE RENAL RESPONSE TO PARATHYROID HORMONE

The effect of thyroid status on renal adenosine 3', 5'-cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex.

Effect of thyroid status on spontaneous and induced surges of luteinizing hormone.

This study was designed to describe the effects of thyroid status on the preovulatory surge of LH and to determine the site(s) at which these effects are exerted. The treatment of normal 4-day cycling rats with a hyperthyroid dose of thyroxine (T4, 20 mug/100 g BW/day) for 8 days resulted in surges of LH on proestrus which were depressed to 25% of control levels. In ovariectomized (OV) or ovariectomized-thyroidectomized (OV-Tx) rats maintained on a physiological regimen of T4 (2 mug/100 gBW/day), the amount of estrogen required to induce an LH surge was far greater than that required in OV-TX rats receiving no T4 replacement. These data suggest that T4 attenuates preovulatory surges of LH by acting at the hypothalamic-pituitary axis. However, the pituitary might be eliminated as a site of action since hyerthyroid proestrous rats responded to a challenge of LH-releasing hormone (500 ng) by secreting a quantity of LH equivalent to that in euthyroid animals. Similarly, there was no difference in the quantity of LH released by hyperthyroid and euthyroid proestrous rats in response to electrochemical stimulation (100 muA, 60 sec) of the medial preoptic area of the hypothalamus. On the other hand, hyperthyroid rats secreted significantly less LH in response to stimulation of the arcuate nucleus-median eminence area (ARN-ME) than did controls. Thus, T4, apparently modifies LH release by depressing the response of the ARN.

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.