Increase In Thyroid Weight Research Articles

Effect of Common Vegetables on Thyroid Function in Rats-A Preliminary Study

Goitrogenic potency of some vegetables of Delhi were studied in rats. Adult male rats were fed separately on thiouracil, thiocyanate and extracts of carrot, cabbage and turnip procured from Delhi market for 26 days. Cabbage and turnip showed high thiocyanate contents while carrot did not show any measurable amount. Appreciable increase in thyroid weight to body weight ratio, plasma thiocyanate, plasma/sup 131/1 contents and protein bound/sup 131/ 1 or plasma were observed in all groups of experimental, rats, except carrot. Results indicated goitrogenic nature of cabbage and turnip in rats.

Effects of sulfonamide on the pituitary-thyroid gland. 1. Morphological changes of thyroid gland and variation in plasma thyroxine and triiodothyronine.

Morphological changes of the thyroid gland on light and electron microscopy as well as concomitant variation in plasma T3 and T4 levels after oral treatment with sulfonamide at a dose of 2 g/kg for 30 consecutive days were examined in male Wistar rats. Several rats were treated with the same dose by the same route for 15 days and then put to the restoration experiment for 15 days. Plasma T3 and T4 levels significantly decreased as compared with the control in the period from the 1st day to the 30th day of the administration. A significant increase in thyroid weight was seen from the 15th day. On the 30th day, the weight was at last about eight times as heavy as that of the control. Histologically, hyperplasia of the follicles which were lined with high columnar cells was observed. The epithelial cells showed considerable pleomorphism and colloid was virtually absent at this time. As early as on the 3rd or 5th day, the follicular cells were high-columnar in shape on electron microscopy and there was an increase in rough-surface endoplasmic reticulum, the cisternae of which were dilated. Swelling of mitochondria and the absence of colloid were also noted. There were no secretory granules in the cytoplasm and numerous long microvilli projected into the lumens. On the 30th day, the follicular cells became remarkably high-columnar and had small and ovoid nuclei at their base. In the restoration study, numerous dense secretory granules and colloid droplet profiles appeared in the cytoplasm.

Desensitisation of rat thyroid to the growth-stimulating action of TSH during prolonged goitrogen administration. Persistence of refractoriness following withdrawal of stimulation.

Abstract. We have previously shown that administration of goitrogen to the rat leads to a sustained elevation of serum TSH but to only a short-lived burst of mitotic activity in the thyroid, growth eventually ceasing after a few months. This work investigates the possibility that this progressive desensitisation may result simply from continued exposure to high levels of TSH and examines the effect of a period of interruption of goitrogen treatment on the sensitivity of the gland to subsequent TSH stimulation. Rats were treated with the goitrogen aminotriazole (ATA) for an initial period of 80 days to reach the plateau of thyroid growth. ATA was then withdrawn for 25 days and subsequently re-introduced for a further 35 days. Animals were killed in groups of 8 at frequent intervals and the following measurements carried out: — Serum TSH, T3 and T4, thyroid weight, follicular cell number and mitotic activity. The initial period of ATA treatment led to a 5-fold increase in serum TSH, a 10-fold increase in thyroid weight and a 9-fold increase in follicular cell number. Mitotic activity stabilised at a few times control levels. Following withdrawal of ATA, TSH and mitotic activity fell to below normal. Thyroid weight fell by 66% but there was no significant fall in follicular cell number. Re-introduction of ATA simply led to a return of all variables to their previous 'stimulated' levels. There was no second burst of mitotic activity and no renewed thyroid growth. The results show that the desensitisation of follicular cells to the growth-stimulating action of TSH following prolonged stimulation is not reversed by withdrawal of the stimulus, and is therefore unlikely to be mediated by a 'downregulation' at receptor or post-receptor level of the type observed for functional responses in vitro. Other possible mechanisms are discussed.

Mast cell hyperplasia during goitrogen-induced thyroid growth - a quantitative study.

This paper describes the effect of long-term goitrogen-administration on the mast cell population of the rat thyroid. Animals were treated with the goitrogen aminotriazole at a dose sufficient to block thyroid hormone synthesis completely, and compared after 80 days with a control group. Serum TSH was measured by radioimmunoassay, and mast cell number quantified from specially-stained tissue sections using appropriate serological methods. Goitrogen treatment led to a 9-fold increase in serum TSH and an 8-fold increase in thyroid weight. Mast cell number per unit volume of thyroid decreased, but total numbers per gland increased 4 to 5 fold. There was a significant fall in mean mast cell size. The work demonstrates conclusively that mast cell hyperplasia occurs during goitre formation and provides a method for its quantitative assessment. The possible mechanisms and significance of thyroid mast cell proliferation are discussed.

Divergent phases of responsiveness of thyroid hormone biosynthesis to exogenous thyroid-stimulating hormone in the postnatal rat.

We have found that the thyroids of postnatal rats respond to administration of thyroid-stimulating hormone (TSH) by significant changes in iodine metabolism and hormone biosynthesis. The specific activity of iodine in thyroxine (T4) and 3,5,3′-tri-iodothyronine (T3) was always higher than that in monoiodotyrosine (MIT) and di-iodotyrosine (DIT) in the TSH-treated rats. The highest sensitivity to TSH in this regard was observed during week 2 of life and again at sexual maturity. The lowest thyroid response to TSH with respect to biosynthesis of MIT, DIT, T4 and T3 was observed in weeks 3 and 4 of life rather than in the younger or older rats. However, the specific activities of MIT and DIT were not changed after TSH administration to 2-day-old pups. Increase in thyroid weight and in the specific activity of iodine in the thyroid occurred in almost all of the TSH-treated rats. In contrast, the thyroid iodine content decreased after TSH administration, except in the 2-day-old pups. The specific activity of iodine in the thyroid was highest in the 2-day-old pups and then abruptly declined during week 1 of life and continued to do so until maturity. The thyroid protein content decreased during the first 2 weeks of life but thereafter it was increased in the rats receiving TSH. We conclude that thyroid responsiveness to TSH in terms of thyroid hormone metabolism has several distinct phases in postnatal rats: the first phase, during week 1 of life is characterized by the highest specific activity of iodinated compounds in the thyroid and by the highest percentage representation of T4 and T3; the second, during week 2 of life, by the highest thyroid response to TSH; the third, during weeks 3 and 4 of life, by the lowest thyroid response to TSH; and the last phase in mature rats is characterized by a relatively low specific activity of iodinated compounds in the thyroid but by a good response to TSH stimulation

Interrelationships among blood pressure, renal function, thyroid activity and renal thyroid depressing factor in renal hypertensive rats.

Renal hypertension in rats was accompanied by both a decrease in thyroid activity (i.e., decreased total serum triiodothyronine concentration, increased serum thyroid-stimulating hormone concentration and increased thyroid weight) and renal function (i.e., reduced renal concentrating ability, increased blood urea nitrogen and serum creatinine concentrations). Systolic blood pressure, thyroid activity and level of renal function of individual hypertensive rats correlated significantly with the content of a thyroid-depressing factor in their kidneys. The results suggest, but do not prove, that a factor released by the kidneys during elevation of blood pressure and/or reduction in renal function may reduce thyroid function in the rat.

Role of the sympathetic nervous system in the control of the goitrogenic response in the rat.

The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to superior cervical ganglionectomy (SCGx) 7 days earlier. In the first experiment, superior cervical ganglionectomized (SCGx) or sham-operated animals were treated with the goitrogenic agent methylmercaptoimidazole (MMI) for 4 days, and their thyroid weights and plasma TSH levels were measured. After MMI administration, the increase in thyroid weight was significantly greater in SCGx than in sham-operated rats. The plasma TSH increases after MMI were similar in both groups. To rule out the possible involvement of the pineal gland, MMI treatment was carried out in rats subjected to pinealectomy or sham pinealectomy 7 days earlier. Thyroid weights and plasma TSH levels after pinealectomy were not different from controls in vehicle- or MMI-treated rats. In a third experiment, the goitrogenic response to TSH was assessed in SCGx or shamoperated rats; the thyroid weight of SCGx anima...

Dependency of Maximum Goitrogenic Response on Some Minimal Level of Thyroid Hormone Production

Thyroidal activity was studied in chicks given dietary thiouracil in conjunction with daily doses of thyroxine and with diets adequate and deficient in iodine. DL-thyroxine administered at doses up to 1.0 μg per day for 10 to 12 days had no effect or slightly increased thyroid weight. Both the epithelial and colloid components of the thyroid gland were increased in response to thiouracil and to thiouracil in combination with low dosages of exogenous thyroxine. Radioiodine uptake was increased above the control with thiouracil and with thiouracil in conjunction with .5 and 1.0 μg DL-thyroxine given daily. Birds receiving thiouracil, with and without exogenous thyroxine, showed a different pattern of radioiodine uptake and release than the control birds. Thiouracil-treated birds showed a rapid uptake of iodine following its administration, which was followed by a rapid decline immediately after peak accumulation, whereas in control birds thyroidal radioiodine concentration reached a plateau at the maximum concentration attained. The goitrogenic response to thiouracil was much greater when the diet was supplemented with iodine than when the diet was iodine-deficient. Thyroids under iodine deficiency contained greater percentages of epithelial tissue than with iodine-supplemented diets. Thyroid glands of chicks given thiouracil in an iodine-supplemented diet contained much more colloid than glands from iodine-deficient chicks with or without thiouracil. DL-thyroxine at a dosage of .5 μg per day to chicks given thiouracil in an iodine-adequate diet increased, whereas higher dosages decreased thyroidal colloid. It is concluded that some minimal concentration of thyroid hormone is required for maximum goitrogenic response. It is not clear whether the response is entirely due to an effect on thyrotropin production or whether there is an effect of thyroid hormone on the thyroid gland itself.

Toxicity of fresh poinsettia (Euphorbia pulcherrima) to Sprague-Dawley rats.

Fresh leaves and bracts of poinsettia (Euphorbia pulcherrima) were fed to 46 Sprague-Dawley rats. The animals were observed for 1 week for changes in weight or behavior. The animals were then sacrificed in ether and examined for changes in thyroid and adrenal weights. One group was also examined for damage to the duodenum, jejunum, and ileum. No lesions or other signs of intestinal damage were observed. None of the groups showed any change in behavior or any significant change in body weight or adrenal weight. Only one group showed a significant increase in thyroid weight.

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.

Lipid and carbohydrate metabolism in euthyroid and hypothyroid chick embryo ( Gallus domesticus)

1. 1. The effect of propylthiouracil (PTU)-induced hypothyroidism on carbohydrate and lipid metabolism was studied in the chick embryo. 2. 2. A single dose of PTU (250 μg/embryo) was administered on day 11 and embryos sacrificed on day 20 of incubation. 3. 3. Thyroid glands were significantly enlarged (6 fold) by PTU administration. 4. 4. Increased thyroid weight was associated with growth retardation and decreased plasma thyroxine levels. 5. 5. Plasma glucose level was lower and phospholipids were significantly higher in the hypothyroid embryo. 6. 6. Liver lipid concentrations in the control and hypothyroid embryos were not different but were significantly higher in both groups when compared to previously reported values in the young chick. 7. 7. In contrast to PTU treatment after hatching, liver glycogen levels were not increased in the hypothyroid chick embryo. This was attributed to the high lipid nutrient condition of the chick embryo since a high lipid diet in the young chick decreased hepatic glycogen accumulation significantly.

Pituitary-thyroid axis during short term, mild and severe, iodine depletion in the rat.

To investigate the most early events occurring during the adaptation of the pituitary-thyroid axis to iodine depletion, two rat populations were submitted to 4 week low iodine regimens of different severity. The variations of the following parameters were studied: pituitary thyrotropin (TSH) concentration, serum thyroxine (T4), triiodothyronine (T3) and TSH, thyroid weight and thyroid iodine concentration. In the first population, mildly iodine depleted, serum and pituitary TSH remained unchanged. The weight of the thyroid increased by the 12th day. Serum T4 dropped by the 26th day. Serum T3 tended to increase during the whole observation period. In the second population, more severely iodine depleted, the increase in thyroid weight appeared by the 4th day. Serum T3 increased from day 13 to day 20, then returned to normal. Serum TSH increased and serum T4 decreased by the 20th day. These results suggest that, in the adaptation to iodine deficiency in the rat, autonomous thyroid regulatory mechanisms play a major role at the onset of goiter growth. On the other hand, most likely a combined effect of serum T3 and T4 triggers variations in pituitary TSH secretion.

THYROID IODINE METABOLISM IN STREPTOZOTOCIN-DIABETIC RATS

ABSTRACT Experiments have been performed to assess the effect of diabetes on thyroid function in male Wistar rats. Diabetes was induced by a single streptozotocin injection. As compared to normals, the diabetic rats displayed: 1) decreased rate of stable iodine uptake by the gland, as measured with a double isotopic technique; 2) decreased in vitro iodide uptake by the thyroid; 3) decreased T/S [I-] ratio after acute treatment with propylthiouracil; and 4) alteration in the distribution of labelled iodoamino acids in the gland. Furthermore, diabetic rats maintained lower plasma TSH levels than normals, in spite of the fact that plasma PBI concentration was slightly but consistently lower in diabetic than in normals, and that the pituitary TSH content was not affected by the lack of normal insulin levels. Injections of TSH (5 U/100 g body weight/day) for 5 days, into diabetic rats caused a return of thyroid function toward normal. Insulin administration resulted in an increase of thyroid weight, an increase of thyroid function, and an increase of pituitary TSH secretion in diabetic rats after the daily injection of 1, 2 or 3 U/100 g body weight/day for 7 days. The decreased pituitary TSH secretion in diabetic rats might involve a disturbance in the feed-back relationship between the thyroid and the pituitary, although other mechanisms could be involved.

Interactions of protein deficiency, cyanide, and thiocyanate on thyroid function in neonatal and adult rats2–3

The effect of protein deficiency or administration of antithyroid drugs or both on the thyroids of suckling and weanling rats was examined. Addition of cyanide or propylthiouracil to a 2% casein low iodine diet for weanling rats resulted in an increase in thyroid weight and a significant increase in plasma thyroid stimulating hormone. The effect of cyanide was eliminated by addition of iodine to the diet and was not apparent when the animals were fed a 20% casein diet. Addition of thiocyanate (SCN−) to the drinking water of iodine deficient gravid rats resulted in the appearance of goiters in both the mothers and their 5- and 10-day old progeny. Studies with 35SCN− in these animals indicated that the concentration of plasma 35SCN− decreased when exogenous SCN− was provided; the fractional transfer of 35SCN− into their milk and to the pups decreased, as did the conversion of 35SCN− to 35SO4−. In adult male rats addition of thiocyanate to the ration increased renal disposal of both labeled and stable SCN−. These findings are consistent with saturation of renal tubular reabsorption and metabolism of SCN−. These studies support the proposition that cyanogenic glycosides and thiocyanate may affect thyroid function in the neonatal iodine deficient rat. They do not support the hypothesis that protein deficiency is a major factor in the responses of the thyroid to iodine deficiency or goitrogens.

THE EFFECT OF STREPTOZOTOCIN-INDUCED DIABETES ON THE PITUITARY-THYROID AXIS IN GOITROGEN-TREATED RATS

ABSTRACT Studies of pituitary and thyroid function have been carried out in normal (intact) and diabetic Wistar rats. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). The animals were fed a low iodine diet (LID), and received a daily sc injection of either KClO4 (20 mg/100 g body weight) or propylthiouracil (PTU) (1.5 mg/100 g body weight) to induce hypothyroidism. Control groups received the same LID but supplemented with 0.8 μg I/g dry weight. In intact rats goitrogen-treatment induces an increase in thyroid weight and in plasma TSH concentration. However, the plasma TSH response to goitrogen-treatment in diabetics indicates that pituitary TSH secretion increases following a reduction in plasma PBI, but the response is less marked than in controls. The difference in plasma TSH between control and diabetic rats provides an explanation for the findings that diabetes diminishes the thyroid growth response to goitrogen-treatment. Moreover, in intact rats the low pituitary TSH content is a consequence of the increase in pituitary TSH secretion, while in the diabetics the low pituitary TSH content cannot be explained by an increase in TSH secretion. The effect of diabetes on the pituitary-thyroid axis cannot be attributed specifically to poor growth, because the changes in pituitary-thyroid function which are observed in the diabetic groups are not seen in intact rats with a growth rate similar to that of insulin deficient rats. Insulin administration to goitrogen-treated diabetic rats results in 1) an increase in the ability of the thyroid tissue to respond to its trophic hormone, 2) an increase in pituitary TSH secretion in response to the lowering of plasma PBI and, 3) an increase in thyroid growth response to goitrogen-treatment. Results are discussed in relation to the assumption that the lack of adequate insulin levels, or its metabolic defects, diminishes the full response of the thyroid to TSH, and affects the pituitary TSH secretion probably as a consequence of altered hypothalamic control of the pituitary function.

Effect of normalization of hypometabolic state on blood pressure in spontaneously hypertensive rats and in patients with essential hypertension.

Spontaneously hypertensive rats (SHR) manifest a hypothyroid state as evidenced by increased thyroid weight, an increased level of plasma thyroid-stimulating hormone (TSH) and a decreased level of plasma thyroxine (T4) and triiodothyronine (T3). In 18 patients with essential hypertension, plasma TSH, T4 and T3 concentrations were all within the normal range, but the T4 level was significantly lower than in the controls. Among 21 hypothyroid patients, 2 had essential hypertension. Administration of thyroid hormone brought the metabolic state to normal in SHR and in hypothyroid patients but failed to affect the blood pressure. It is suggested that abnormality of thyroid function is neither the cause nor the accentuating factor in the development of hypertension in SH rats and in man.

Thyroid changes in PCB-dosed guillemots and their indication of one of the mechanisms of action of these materials

A group of six guillemots Uria aalge, reared in the laboratory, were fed daily doses of PCB (Aroclor 1254) for 45 days at dose rates from 12 to 400 mg/kg/day. A further three birds were maintained as controls. The birds given 12 and 25 mg/kg/day showed increased thyroid weight, follicle size and colloid area. Increasing the dose rates further produced significant dose-related decreases in these parameters until, in the bird which died at 400 mg/kg/day, the thyroids showed atrophy with only 59·6% of the weight and 27·3% of the total colloid area of the controls. These changes suggest a direct effect of the PCB on the avian pituitary, causing a dose-related decrease in the amount of thyrotrophin produced. The large colloid goitre seen at 12 mg/kg/day suggests involution as thyroid hormone depletion is reduced; this is changed to atrophy when TSH production by the pituitary ceases. A dose-related reduction in pituitary weight supports this conclusion. These thyroid changes suggest that PCB-dosed birds would be in a state of hypothyroidism. This action on the pituitary producing secondary hypothyroidism could be one of the main sub-lethal lesions of these materials and could be the mechanism behind many of the sub-lethal effects noted in the literature. The thyroid changes already noted in PCB-dosed lesser black-backed gulls Larus fuscus suggest that guillemots may be much more sensitive to PCB than this species in that they exhibit the same effects more than twice as rapidly.

The effect of prolonged Kale feeding on the thyroid glands of sheep

Four groups of sheep were fed the following rations: Group I Kale ad lib., Group II Kale ad lib.+0·22 kg. blood meal/flaked maize mixture, Group III Kale ad lib.+0·22 kg. blood meal/flaked maize mixture and 10 mg. Kl weekly by mouth, Group IV 0·9 kg. hay+0·22 kg. blood meal/flaked maize mixture. They were fed these rations for 17 weeks when the sheep were killed. The thyroids were removed, weighed and pieces were taken for histological examination. The kale had a goitrogenic effect which was overcome by the iodine supplementation. The group receiving kale showed only a three-fold increase in thyroid weight whereas the group receiving the blood meal/flaked maize mixture in addition to the kale showed a six-fold increase in weight. The mixture had no goitrogenic effect when fed without kale to the control group. The mixture appears to increase the goitrogenicity of the kale. The histology shows considerable hypertrophy of follicular epithelial cells and a diminution in colloid and this accounts for the weight incrase of the glands.

Acute and short-term toxicity studies on erythrosine BS in rodents

The 7-day LD 50 values for Erythrosine BS were similar in both sexes of rats and mice at 6·7–7·4 g/kg after a single oral administration and 0·32–0·40 g/kg following an ip injection. Erythrosine BS was given to groups of 15 male and 15 female rats at dietary concentrations of 0 (control), 0·25, 0·5, 1·0 or 2·0% for 13 wk. There were no effects attributable to treatment on the rate of body-weight gain, food intake, results of haematological examinations, serum analyses or renal function tests. The main findings in the study were caecal distension at all treatment levels, an increase in thyroid weight and pigmentation of the kidney tubules. The pigmentation was found in both sexes at the highest level and in males given 0·5 or 1·0% Erythrosine BS. The no-untoward-effect level was 0·25% of the diet, equivalent to an intake of 160–170 mg/kg/day.

Relation Between Thyroid Iodine Content and the Accumulation and Oxidation of [35S]Methimazole in the Rat

The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.