Low Iodine Diet Research Articles

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.

Increase in the rough endoplasmic reticulum in capillary endothelial cells and pericytes in hyperplastic rat thyroid glands.

Observatios were made on the rough endoplasmic reticulum (RER) of the blood capillary endothelium, pericytes, and lymphatic endothelium in the course of studies of changes occurring in the thryoid gland during the development of thyroid hyperplasia. To induce the hyperplasia, Fischer rats were fed a goitrogen (thiouracil) an a low iodine diet for various time intervals from 3-100 days. Thyroid glands were fixed by perfusion with glutaryldehyde and embedded in Epon. A noticeable increase in the RER in the capillary endothelium was seen by 3 days. This increase was very pronounced by 7 days and persisted in many cells at 100 days. The RER response was also pronounced in pericytes. In the lymphatic endothelium, however, the increase in RER was barely perceptible. These results suggest that capillary endothelium and pericytes have protein synthetic and secretory functions of an unknown nature that become strongly activated in stimulated thyroid glands.

Ultrastructural aspects of capillary fusion during the development of thyroid hyperplasia

When young adult male Fischer rats are fed a low-iodine diet containing 0.25% thiouracil the blood capillaries enlarge and appear to fuse, with the temporary appearance of partial septa between capillary lumina. The mechanism of the fusion was examined by electron microscopy. The partial septum was made up of intact cells with a tight junction near its distal end. A mechanism to form such partial septa must involve the penetration, by endothelial cells, of two basal laminae and a collagen layer between the capillary walls. The penetration may be made by pseudopods on the abluminal surface of many endothelial cells, about half of which penetrated basal laminas. The fusion may involve pairs of pseudopods at cell margins. Multiple small fusion sites between neighboring walls of parallel capillaries observed in serial sections may be an intermediate stage in capillary fusion. Aggregates of blood platelets were observed near collagen exposed when endothelial cells retracted.

Conformational change of the thyroglobulin molecule induced by oxidation in vitro

Previous election-microscopical studies from this laboratory have shown that the thyroglobulin molecule can occur in two different conformations, one ovoid and the other cylindrical. Ovoid molecules are characteristic of well-iodinated thyroglobulin whereas cylindrical molecules are found after low-iodine diet or blocking of iodination. The present study was performed in order to elucidate the possible relation between the molecule conformation and the peroxidase-catalyzed reactions that occur in the thyroid in connection with hormone synthesis. Cylindrical thyroglobulin molecules (from PTU-exposed thyroids) were incubated in different media and the proportion of cylindrical and ovoid molecules after incubation was estimated in electron micrographs. It was found that incubation with glucose-glucose oxidase caused an extensive conversion of cylindrical molecules into ovoid molecules. Peroxidase and/or iodide were not necessary for this change of conformation. It is suggested that this in vitro molecule transformation was the result of an oxidation reaction.

Induction of Sustained Hyperthyroidism and Hypothyroidism in the Turkey: Physiological and Biochemical Observations

In order to study the role of thyroid hormone in avian physiology, reliable methods for inducing sustained states of hyperthyroidism and hypothyroidism in the turkey were developed. Hyperthyroidism was established by administration of L-thyroxine ( 3 μg/ml) to the drinking water. Hypothyroidism was established either by the provision of a low-iodine diet and supplementation of the drinking water with .5% sodium perchlorate, or by the intravenous administration of an ablative dose (10 mCi) of 131I−. Clinical manifestations of hyperthyroidism and hypothyroidism were accompanied by high (10.1 ± 1.4 μg/dl) or low (.34 ± 0.04 μg/dl) plasma concentrations of thyroxine, respectively, both significantly different from normal controls (.57 ± .08 μg/dl; P<.05). Among the objective manifestations were striking differences in basal body temperatures in the hyperthyroid, normal, and hypothyroid groups: 41.0 ± .12 vs. 40.5 ± .06 vs. 39.8 ± .10 C, respectively (P<.002). Hyperthyroidism was also associated with decreased total serum lipids, cholesterol, and uric acid, whereas hypothyroidism was associated with significantly increased serum levels of cholesterol, uric acid, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactic dehydrogenase, and creatine phosphokinase. The following serum parameters were similar among all groups of turkeys: calcium, phosphorus, blood urea nitrogen, creatinine, total protein, albumin, sodium, chloride, glucose, alkaline phosphatase, γ-glutamyl transpeptidase, triglycerides, bilirubin, and iron. Circulating catecholamine levels were also unchanged (14 to 23 nM) among the three groups of birds.

Low-iodine diet for producing iodine deficiency in rats.

A low-iodine diet has been prepared for rats, using locally available low-iodine ingredients. On analysis it has been shown to consistently contain 15-20 ng iodine/g. When fed to growing female rats, this diet produced severe iodine deficiency while not significantly affecting growth or reproduction. The deficiency was manifested by a fall in daily urinary iodine excretion (to less than 1 microgram/day) and a seven-fold increase in thyroid uptake (131I) observable within 3 months. Levels of plasma thyroxine (T4) and thyroid stimulating hormone (TSH) continued to change for 4-5 months, T4 falling from 69.9 to 7.5 nmol/l and TSH increasing seven-fold from a control value of 364 to 2406 ng/ml. Goitre was present in all iodine-deficient rats and iodine content in the thyroid was 10% of the control value.

Production of Severe Iodine Deficiency in Sheep Using a Prepared Low-Iodine Diet

Extensive tests on dietary materials suitable for ingestion by sheep have led to the preparation of an appropriate diet which, when fed to the sheep, caused severe iodine deficiency. The deficiency was manifested by daily urinary excretion values which fell to levels of less than 20 micrograms iodine and by thyroxine (T4) and triiodothyronine (T3) concentrations in blood plasma which were reduced from more than 90 and 1.80 nmol/l to the low levels of less than 2.58 and 0.31 nmol/l respectively. The values were attained 5 months after feeding the low-iodine diet. Goitre was present in most of the animals and the reductions in T4 and T3 values were accompanied by increased concentrations of plasma thyroid stimulating hormone (TSH) from less than 8.6 to more than 68 ng/ml. Samples of wool removed from selected areas of the sheep showed that the iodine-deficient diet also caused a reduction in the growth of wool.

Growth and development of the neonatal rat: particular vulnerability of males to disadvantageous conditions during rearing.

Rat pups were nutured on radioactive iodine-containing milk by dams fed low-iodine (Remington) diets plus sodium 125I-iodide (Na 125I) supplements from 3 days before parturition to the time of weaning. Effects of individual features of this experimental regimen on developmental progress of the offspring were examined. Nutritional deficiencies inherent in the maternal Remington diet did not alter growth rate, if the pups were only minimally disturbed in the course of rearing. However, when combined with chronic handling stress (itself having no detectable effect on the weight gain of pups normally fed mothers), growth retardation was noted, without evidence of hypothyroidism. Addition of Na 125I to the maternal Remington diet reduced the growth rate of non-handled animals only. The strategy of measuring post-weaning catch-up growth served to magnify latent signs of pre-weaning growth retardation and revealed that males were more susceptible than females to early dietary deficiencies, radiation and handling stresses.

INFLUENCE OF IODINE ON THE FORMATION OF 27S AND LARGER IODOPROTEINS IN RAT THYROID FOLLICLES

SUMMARY The importance of the presence of iodine for the formation of iodoproteins larger than 19S thyroglobulin, i.e. 27S and larger iodoproteins (large-TG), was studied. Samples of colloid were collected in vivo by micropuncture of single rat thyroid follicles after treatment with a low iodine diet or potassium perchlorate. The protein composition of the colloid was analysed by microgel electrophoresis on polyacrylamide gels. It was observed that the large-TG fractions were reduced by approximately 50% after treatment with a low iodine diet for 3 months. The large-TG fractions were almost absent after treatment with perchlorate for 3 weeks. Administration of 5 or 10 μg potassium iodide to the animals on a low iodine diet resulted in a significant increase of the relative amount of the large-TG fractions in the colloid within approximately 2 h, the higher dose of KI producing a more pronounced accumulation of the large-TG fractions. Inhibition of protein synthesis by cycloheximide did not prevent the increase of large-TG proteins in animals on a low iodine diet after the administration of 5 μg KI. The administration of iodide to rats treated with potassium perchlorate did not result in the appearance of large-TG fractions. It is concluded that the aggregation of thyroglobulin molecules occurs in the follicle lumen as a consequence of iodine administration. This formation of large-TG fractions does not require exocytosis of newly synthesized protein.

Effect of PTU added to a low iodine diet on peroxidase activity and other parameters of thyroid function in rats.

ABSTRACT The evolution of peroxidase activity was followed in relation to other parameters of thyroid function in rats when PTU was added to a low iodine diet (LID). Ten days of PTU treatment brings about an equivalent increase in thyroid weight and iodide peroxidase activity at whatever time PTU was added to LID (10, 35, 54 and 80 days). It is shown that the effect of PTU treatment on thyroid weight and peroxidase activity is proportionately higher when PTU is added after 10 days of LID alone than after 80 days. The effect of various durations of PTU treatment was studied more closely when the addition began on day 10 of LID. On day 1 after addition of PTU thyroid weight increased significantly and no significant change was found in peroxidase activity. In contrast 5 days of PTU induced a significant elevation in enzymatic activity which is greater than that of thyroid weight. For a longer period of PTU treatment (10 days or more), the per cent increase of thyroid weight and peroxidase activity evolved parallely. Already on day 1 of PTU treatment very rapid change were noted on T4, T3 and TSH levels; there was a decrease in T3 level (26 ± 5.6 %), while an increase in T4 level (26.4 ± 4.7 %) and TSH level (30 ± 5 %) was observed when the iodine content was still high (about 11 μg/thyroid gland). Thereafter T3 and T4 decreased and stayed at the same level after 10 days of PTU, while TSH increased rapidly and reached a plateau between 18 and 35 days. When PTU was added to LID treatment the increase in TSH was mostly due to a decrease of T3. The per cent increase in serum TSH level is always higher than that of thyroid peroxidase activity.

The Goitrogen 3-Hydroxy-4(1H)-Pyridone, a RuminaI Metabolite From Leucaena Leucocephala: Effects in Mice and Rats

Mice fed a diet containing 1% (w/w) 3-hydroxy-4(1H)-pyridone (DHP) developed goitre even with a diet high in iodine whereas mimosine (0.5% w/w) did not produce goitre even with a low-iodine diet. Thyroid enlargement was apparent (measured morphometrically) by the 7th week and was advanced by the 11th week. Histologically the goitre was hyperplastic in type. No marked histological changes were found in other organs of mice fed DHP or any organs of mice fed mimosine, except for some atrophy of hair follicles. A single intragastric dose of DHP inhibited the uptake of 125I by the thyroid in the rat but an equivalent dose of mimosine did not. Evidence is presented that the inhibition occurs at the iodine binding step, as with methyl thiouracil, rather than at the iodide trapping step, as with thiocyanate. Chronic treatment of mice with DHP, as with 6-methyl thiouracil, increased the avidity of the thyroid in taking up 125I. The major conjugated form of DHP in mammals, DHP-3-O-glucuronide, was almost as effective a goitrogen as the unconjugated compound when given by mouth but considerably less active than the free form in the blood stream. It was concluded that DHP is a potent antithyroid compound of the thiouracil type with low general toxicity, since mammals can tolerate a level of intake sufficient to produce goitre in spite of iodine supplementation.

Mechanism of action of thioureylene antithyroid drugs: factors affecting intrathyroidal metabolism of propylthiouracil and methimazole in rats.

Experiments were performed with rats to test the physiological significance of a previously proposed mechanism of action of thioureylene antithyroid drugs, which had been derived from results obtained with a model system containing purified thyroid peroxidase. Two features of the previously proposed scheme were tested:1) the effects of drug dosage and 2) the effects of iodine deficiency. In the dosage experiments, rats were injected with graded doses of [35S]PTU (0.18-59 mumol or [35S]mmi (0.16-18 mumol). Thyroid glands were removed 1 and 6--8 h later and 35S distribution in the homogenates was determined by paper chromatography. Serum samples were also analyzed by the same procedure. From the measured 35S activity in the various components and from the known specific activity of the injected drugs, it was possible to calculate thyroidal concentrations of unchanged drug and drug metabolites. At low doses, thyroidal concentrations of unchanged 6-propyl-2-thiouracil (PTU) and 1-methyl-2-mercaptoimidazole (MM) significantly exceeded their concentrations in serum, as reported by previous investigators. A major new finding in the present investigation was the observation that intrathyroidal metabolism of PTU and MMI is greatly affected by dosage. Marked inhibition of intrathyroidal drug metabolism was observed at 6-8 when the dosage was increased from 5.9 to 18 mumol for [35S]PTU and from 0.88 to 2.2 mumol for [35S]MMI (per 200 g rat). These findings demonstrate that with increasing dosage, PTU and MMI inhibit their own intrathyroidal metabolism. These dosage effects are similar to results previously reported for in vitro oxidation of PTU and MMI by the thyroid peroxidase system, and they offer support for the physiological significance of the previously proposed scheme. Further evidence for the physiological validity of this scheme was obtained in the experiments with iodine-deficient rats. As predicted from the in vitro findings, intrathyroidal metabolism of [35S]PTU and [35S]MMI was markedly reduced in rats on low iodine diet.

Blood capillary enlargement during the development of thyroid hyperplasia in the rat.

To study blood capillary growth in the hyperplastic thyroid gland, rats were fed 0.25% thiouracil in a low iodine diet for time intervals up to 100 days. Thyroids were fixed by vascular perfusion and embeded in Epon. Whole lobes were sectioned from pole to pole and slides were prepared of sections every 0.3 mm. Capillaries were clearly enlarged by 3 days and they enlarged progressively thereafter. By 3 days, the cells of many neighboring capillaries came into close apposition and from this time on, there was evidence of fusion of capillary walls in the form of partial septa in the capillary lumens. Fusion continued until 20 days, when follicles were almost completely surrounded by a continuous endothelial sheet and unfused capillary walls were separated by connective tissue. The vascular pattern around peripheral follicles changed in a way similar to interior follicles, except that in places, capillaries were gradually excluded from the space between epithelium and thyroid capsule. Vascular enlargement was restricted to the thyroid blood vessels. There was no obvious enlargement of the blood capillaries of the parathyroid despite its close proximity to the thyroid.

Regulation of the uterine response to estrogen by thyroid hormone.

After estradiol (E2) administration, early increases (within 4 h) in uterine wet weight and the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose are similar in ovariectomized rats and in ovariectomized rats made hypothyroid by feeding a low iodine diet containing prophylthiouracil. Most late uterine responses occurring 24 h after E2 treatment, however, are greatly diminished in the hypothyroid animals. The diminished responses include increases in uterine wet weight, dry weight, protein content, RNA content, and the incorporation of thymidine into uterine DNA. One response, the synthesis of 2-deoxyglucose-6-phosphate from 2-deoxyglucose is not diminished in hypothyroid rats 24 h after E2 treatment. The diminished uterine response is not due to a shift in the dose-response curve for E2, but results from a decrease in the magnitude of the maximum uterine response. Treatment of hypothyroid rats with exogenous T3 restores the diminished uterine response in a dose-dependent and time-dependent manner. A dose of 0.5 microgram T3/100 g BW for 5 days restores the response completely, while 48-72 h of treatment with higher doses of T3 are required to restore the response. The effect of T3 is not mediated by the pituitary, since exogenous T3 restores diminished uterine responses in ovariectomized, hypophysectomized animals. These results suggest that thyroid hormones may have a direct effect on the uterus which regulates the responsiveness of the organ to E2.

Metabolism of thyroid hormones by rat thyroid tissue in vitro.

Rat thyroid lobes or hemilobes have been incubated in Krebs-Ringer phosphate buffer containing labeled T4 and/or T3, and the products were separated by paper chromatography. Labeled T4 was actively degraded; about half of the T4 metabolized was recovered as T3. Labeled T3 was also metabolized, but less rapidly than T4. Other than T3 produced from T4, the major products from both hormones were inorganic iodide and iodoprotein; the latter was presumably a secondary product of iodide organification because its formation was inhibited by hypoxia and methimazole. Feeding the animals a low iodine diet increased their hormone-metabolizing activity. Incubation under nitrogen did not affect the rate of T4 degradation, but partially inhibited T3 degradation. Degradation of both hormones was unchanged in the presence of methimazole and ascorbate, was markedly inhibited by 1 mM propylthiouracil (PTU), and was partially inhibited by azide and cyanide. Thyroid tissues concentrated both hormones, tissue to medium gradients averaging 5.4 for T4 and 20.7 for T3; none of the conditions affecting hormone degradation (incubation under nitrogen or with azide, cyanide, or PTU) significantly altered these gradients. It is concluded that the thyroid can metabolize both of its major hormones by a system distinct from thyroidal peroxidase. Hormone metabolism, therefore, is a potentially important factor in net hormone secretion. In its resistance to hypoxia, methimazole, and ascorbate and its sensitivity to PTU, the thyroid's system for generating T3 from T4 resembles T3-forming systems of liver and kidney. The thyroid, because T3 formation is its dominant pathway for T4 metabolism, may provide a useful model for study of this reaction.

Comparison of pituitary-thyroid maturation in the fetuses of rats fed an iodine-deficient or normal diet.

From the earliest detectable development of fetal pituitary-thyroid function (day 18-19 of gestation) through the first postnatal day, there was a higher degree of stimulation of the pituitary-thyroid axis in the fetuses of rats fed a low iodine diet (LID) than in those of rats fed a high iodine diet (HID). Significant differences between the two groups were consistently observed in relative thyroid size, plasma TSH, 4-h thyroid radioiodine uptake, and the labeled iodoamino acid composition of thyroid digests. Plasma T4 concentration was lower in both LID and HID fetuses and pups than in the HID mothers. Plasma T3 was not detectable (less than 20 ng/dl) in the fetuses of either group, nor was labeled T3 in the thyroid digests. Body weight, plasma T4, and pituitary TSH content were usually lower in the LID than the HID animals of comparable age; however, these differences were not consistently statistically significant (P less than 0.05). We conclude that iodine deficiency causes a marked stimulation of TSH secretion and, consequently, of thyroid growth and metabolism from the earliest development of fetal pituitary-thyroid function.

Changes of the hypothalamus-pituitary-thyroid axis in streptozotocin-diabetic rats during adaptation to a low iodine diet.

ABSTRACT Studies on the hypothalamus-pituitary-thyroid axis have been carried out in control and in diabetic male Wistar rats during adaptation to a 125I-labelled low iodine diet. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). Thyroid weight, thyroid 127I and 125I content, [125I]iodoamino acid distribution in thyroid digests, plasma PBI, plasma and pituitary TSH and hypothalamic TRH by radioimmunoassay were measured between 5 and 30 days after saline or streptozotocin injection, corresponding to 15 and 40 days after onset of the 125I-LID. As compared to controls, diabetic animals have smaller thyroids. The 125I and 127I in diabetic thyroids between 5 and 10 days was lower than in control glands; at longer intervals both 125I and 127I increased with time in diabetics, while no remarkable changes were seen in the control glands. Furthermore, the percentage of T3 and the MIT/DIT and T3/T4 ratios in thyroids of diabetic were lower than in the corresponding control group at all intervals. These results are compatible with a deficiency of TSH stimulation and/or with a high thyroidal iodine content. Compared to the controls, each group of diabetic rats presented a significantly lower plasma TSH concentration, in spite of the fact that its plasma PBI is more or similarly reduced in diabetic than in controls. Furthermore, the decreased pituitary TSH secretion in diabetic rats at early intervals is lower than in controls although the pituitary TSH and hypothalamic TRH remain within normal ranges. It is concluded that the decrease in pituitary TSH secretion may be the result of a reduction of pituitary TRH stimulation, secondary to a diminished secretion and/or synthesis of TRH by the hypothalamus.

EFFECT OF IODIDE ON THE ADENYL CYCLASE SYSTEM OF THE MOUSE THYROID IN VIVO

ABSTRACT Iodide, administered to mice either acutely or chronically, depressed the thyroidal cyclic adenosine monophosphate (cAMP) response to 20 mU bovine TSH. When iodide was administered acutely there was a 60% reduction in the cAMP accumulation after 100 μg, or 1 μg KI given to mice on normal iodine diet (NID), or low iodine diet (LID), respectively. When iodide was administered chronically by supplementing the LID with graded doses of KI for 11 days, the cAMP response to TSH was found to be inversely related to the dietary iodine. Inhibition occurred after 5 μg KI, a dose similar to the daily iodine intake. Iodide depressed, but did not abolish, the thyroidal cAMP response to TSH. Iodide had no effect on phosphodiesterase activity, whereas thyroidal adenyl cyclase activity was diminished by the prior administration of 100 μg KI. The iodide effect was abolished by pre-treatment with methylmercaptoimidazole i.e. the inhibition is related to iodide oxidation. The newly organified thyroidal iodine (NOTI), formed at 2 h from 0.1–1000 μg KI was determined. The amount of NOTI was highly correlated to the degree of inhibition, irrespective of the iodine content of the diet. This relationship was continuous up to 100 ng NOTI and 70% inhibition, which are the maximal values obtained for NOTI formation and inhibition of cAMP accumulation. These plateau levels were reached with 100 or 1 μg KI in mice on NID or LID, respectively. These results indicate that the inhibitor is an iodinated substance whose intrathyroidal formation is quantitatively parallel to, or a part of NOTI.

Metabolic response to short periods of starvation in hypo- and hyper-thyroid male rats.

1) Thyroidectomized rats were fed with a low iodine diet, injected daily with 0, 0.1, 1.8 or 25 microgram of L-thyroxine/100 g body wt., and compared with intact controls. 2) Plasma protein-bound iodine was decreased in the rats given the 0 and 0.1 microgram doses, unchanged in those given the 1.8 microgram doses, unchanged in those given the 1.8 microgram dose increased in those given the 25 microgram one. 3) The liver content of DNA-P, phospholipid-P, proteins and fatty acids was decreased in the rats that did not receive thyroxine, practically recuperated in those receiving 0.1 microgram and normal in those given 1.8 or 25 microgram of thyroxine. 4) 3 h of starvation produced a reduction in the liver content of total fatty acids that disappeared after 24 h. 5) When fed, liver glycogen concentration was low in the rats given 25 microgram of thyroxine. 6) With starvation, the fall in liver glycogen and blood glucose, and the rise in liver acetyl-CoA and citrate and blood glycerol concentrations were faster in the thyroidectomized rats that did not receive thyroxine than in the other groups. 7) The rise in plasma free fatty acid and blood ketone bodies concentrations were similar in all the groups, the greater level of the first parameter being observed after 6 h of starvation in the rats given 25 microgram of thyroxine and in the second one after 24 h in the rats given either 0.1, 1.8 or 25 microgram of thyroxine. 8) The rapid decrease in the availability of carbohydrate stores with starvation in the thyroidectomized rats could be responsible for their fast call for lipid utilization. The slower response to fasting in the hyperthyroid animals is probably a consequence of their reduced amount of endogenous substrates to be mobilized.

Relationship between peroxidase activity and serum TSH, T4 and T3 levels in rats in the course of iodine deficiency.

ABSTRACT The relationship between peroxidase activity and serum TSH, T4 and T3 levels was investigated in the course of iodine deficiency in rats. Rats were maintained either on a control diet with a relatively high iodine content (600 μg/kg of 127I), or on a low iodine diet (30 μg/kg of 127I). Twenty days after the low iodine treatment, the thyroid iodine [127I] concentration was half that of control value (647 ± 52 and 1241 ± 72 μg/g of wet weight, respectively). However, no significant changes in serum T4, T3, TSH were found at 20 days even though an early increase in peroxidase activity was observed. It was only at 35 days of iodine deficiency, when the concentration of iodine in the gland averaged 260 μg/g of wet weight that serum T4 and TSH levels started to be significantly modified. From day 35 to day 70, a significant and progressive decrease of plasma T4 concentration was observed, and it levelled off thereafter. The changes of serum T3 were much smaller than those of T4. A significant increase in serum TSH level was noted at 35 days. Thereafter TSH levels increased rapidly and progressively (205 % increase over control at 70 days and 643 % at 80 days). From day 35 until day 80 of the low iodine treatment, the thyroid peroxidase activity and the serum TSH level varied concomitantly. Our results suggest that for an iodine content between 5 and 2 μg per thyroid gland, the high cellular peroxidase activity observed could be correlated with an increase in circulating TSH, due to a decrease of T4. In contrast, in the early period of iodine deficiency, no correlation was found between peroxidase activity and serum T4, T3 and TSH levels.