Goiter In Rats Research Articles

Haizao Yuhu decoctions including three species of glycyrrhiza protected against propylthiouracil-induced goiter with hypothyroidism in rats via the AMPK/mTOR pathway

Ethnopharmacological relevanceGlycyrrhiza and sargassum are among the 18 incompatible medicaments according to traditional Chinese medicine (TCM) theory. Although it contains glycyrrhiza and sargassum, Haizao Yuhu decoction (HYD) is a classic prescription widely used as TCM to treat goiter. According to the Chinese Pharmacopoeia, glycyrrhiza is divided into three varieties: Glycyrrhiza uralensis Fish., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. Whether the three varieties of glycyrrhiza have different efficacy or toxicity when applied in the HYD is unknown. Aim of the studyTo explore whether the HYDs comprising three varieties of glycyrrhiza have different efficacy or toxicity when used to treat goiter in rats and the underlying mechanisms of these HYDs. Materials and methodsFor two weeks, the goiter model was replicated by intragastric propylthiouracil (PTU) administration. Samples were divided into the control group, model group, euthyrox group, HYD with glycyrrhiza uralensis (HYD-U) group, HYD with glycyrrhiza glabra (HYD-G) group, and HYD with glycyrrhiza inflata (HYD-I) group. After four weeks of treatment, body weight, rectal temperature, thyroid/liver/kidney coefficient, thyroid/liver/kidney function, thyroid/liver/kidney histomorphology, and thyroid ultrastructure were evaluated. Then, real-time quantitative reverse-transcription polymerase chain reaction (RTqPCR), Western blot, and immunofluorescence analyses were performed to detect genes and proteins affecting autophagy and apoptosis in thyroid cells in the AMP-activated Protein Kinases (AMPK)/Mammalian target of rapamycin (mTOR) pathway. ResultsAll three HYDs increased thyroid hormones (THs) levels, relieved thyroid pathological tissue and ultrastructure, and activated vital proteins and genes in the AMPK/mTOR pathway. Comparisons among the efficacy of the three HYDs indicated that HYD-U restored the THs most effectively; however, no difference in the anti-goiter effect was observed. Moreover, the three HYDs resulted in no toxicity and promoted the recovery of impaired liver and kidney function caused by PTU. Comparisons among the recovery effects of the three HYDs on the liver and kidney were the same. ConclusionOur experiments demonstrated that the three HYDs had outstanding anti-goiter effects and protected liver and kidney function. Their anti-goiter effects were attributed to AMPK/mTOR pathway-induced autophagy and apoptosis. HYD-U resulted in the best THs recovery. It was further indicated that in our present study, glycyrrhiza and sargassum were compatible in the three HYDs, thereby suggesting their safety of compounding in HYD and providing a basis for the research of the 18 incompatible medicaments.

Subacute toxicity of p,p′-DDT on rat thyroid: Hormonal and histopathological changes

The purpose of this study is to assess the effect of p,p′-DDT on thyroid activity of male Wistar rats. Pesticide was administered intraperitoneally (i.p.) for 10 consecutive days at doses of 50 and 100 mg/kg/day. At the end of the treatment, the endpoints examined included serum total levels of triiodothyronine (T 3), total thyroxine (T 4), and thyroid stimulating hormone (TSH). Thyroid gland histopathology and tissue metabolism of thyroid hormone (T 4 UDP-glucuronyltransferase UDP-GT and 5′-deiodinases) were determined. DDT treatment altered thyroid function namely by increasing hepatic excretion of T 4 glucuronide. At the dose of 50 mg/kg it decreased T 4 circulating levels and increased thyroid 5′-deiodinase type I (5′-D-I) and brown adipose tissue (BAT) 5′-deiodinase type II (5′-D-II) activities but it did not affect liver 5′-D-I activity which might contribute to the maintenance of the serum T 3 level. Treatment with 100 mg DDT/kg decreased serum thyroid hormone concentration and tissue 5′-D-I activity without affecting BAT 5′-D-II activity. Gland histomorphological analysis showed hyperplasia and squamous metaplasia with abundant colloid. These observations associated to the elevated serum TSH levels and gland hypertrophy suggest that DDT exposure induced an hypothyroidism state with a colloid goiter in rats.

Goitrogenic activity of p-coumaric acid in rats.

The effects of three natural phenolic acids (caffeic, ferulic, and p-coumaric) on the rat thyroid gland were examined in a 3-week oral-treatment study. Forty male Wistar albino rats, divided into groups of 10 rats each and fed iodine-rich diet, were administered by gastrointestinal tube saline (control), caffeic acid, ferulic acid, or p-coumaric acid at a dose level of 0.25 micromol/kg/day for 3 weeks. The mean absolute and relative thyroid weights in caffeic, ferulic, or p-coumaric acid groups were significantly increased to 127 and 132%, 146 and 153%, or 189 and 201% compared to control value, respectively. Histological examination of the thyroids of p-coumaric acid group revealed marked hypertrophy and/or hyperplasia of the follicles. Caffeic or ferulic groups showed slight to moderate thyroid gland enlargement. Thyroid lesions in p-coumaric acid group were associated with significant increases in cellular proliferation as indicated by [(3)H]thymidine incorporation. In addition, the goitrogenic effect of p-coumaric acid was further confirmed by significant decreases (50%) in serum tri-iodothyronine (T(3)) and thyroxine (T(4)), and a parallel increase (90%) in serum thyroid stimulating hormone (TSH) compared to control group. These results indicate that administration of p-coumaric acid at relatively high doses induces goiter in rats.

The Pharmacokinetics of Perchlorate and Its Effect on the Hypothalamus–Pituitary–Thyroid Axis in the Male Rat

Perchlorate, an environmental contaminant, is known to disturb the hypothalamus–pituitary–thyroid (HPT) axis by blocking iodide accumulation in the thyroid. Iodide deficiency can lead to hypothyroidism and goiter in rats. The objective of the study was to characterize the pharmacokinetics of perchlorate in male Sprague–Dawley rats relative to inhibition of thyroidal radiolabeled iodide uptake and onset of up-regulation of the HPT axis. Radiolabeled perchlorate (3.3 mg/kg 36ClO − 4) was excreted in urine (99.5% over a 48-h period). 36ClO − 4 is rapidly distributed into tissues with preferential sequestration into skin, gastrointestinal tract (GT), and thyroid. Calculated half-lives of 36ClO − 4 from the skin, thyroid, plasma, GT, and GT contents were 32.0, 7.6, 7.3, 10.0, and 8.6 h, respectively. Perchlorate was very effective at inhibiting thyroidal uptake of radiolabeled iodide ( 125I −). In animals iv dosed with perchlorate followed by an iv challenge of 125I −, thyroidal 125I − uptake was diminished by 11, 29, 55, and 82% at 11 h postdosing in the 0.01, 0.1, 1.0, and 3.0 mg/kg perchlorate dose groups, respectively. In perchlorate drinking water studies, dose-dependent inhibition in thyroidal uptake of 125I − initially occurred with corresponding increases in serum thyroid-stimulating hormone (TSH) levels and decreases in thyroid hormone levels. TSH stimulated recovery from the initial perchlorate blocking effects was evident during 14 days of treatment in the 1.0 and 3.0 mg/kg per day treatment groups. However, recovery of serum thyroid hormones at these doses was much slower despite evidence for iodide sufficiency in the thyroid. These results suggest that the typical homeostatic mechanisms of the thyroid may respond differently at high doses of perchlorate used in this rat study (above 1 mg/kg per day) or perchlorate may be acting on the HPT axis by mechanisms other than thyroidal 125I − uptake inhibition.

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Tie-2 is expressed on thyroid follicular cells, is increased in goiter, and is regulated by thyrotropin through cyclic adenosine 3',5'-monophosphate.

Angiogenesis is coordinated with follicular cell growth in goitrogenesis. The angiopoietins, Ang-1 and Ang-2, are angiogenic growth factors acting through Tie-2, a tyrosine kinase receptor. We have examined the expression and regulation of the angiopoietins and Tie-2 in human and rat thyroids. In human goiters there was increased Tie-2 immunostaining, compared with that in normal thyroids, on both follicular and endothelial cells. In an induced goiter in rats, in situ hybridization showed increased expression of messenger ribonucleic acids (mRNAs) for Tie-2 and Ang-1 in follicular cells. As Tie-2 has previously been believed to be restricted to cells of endothelial lineage in adults, we examined its expression further in isolated follicular cells. Tie-2 and Ang-1 mRNA expression in human thyrocytes was confirmed by ribonuclease protection assay. Ang-2 mRNA was not detected in human cultures or rat thyroids. In both human follicular cell cultures and FRTL-5 cells, immunoblotting showed that Tie-2 expression was increased by TSH and agents that increased intracellular cAMP. In conclusion, we have demonstrated the expression of Tie-2 and Ang-1 in thyroid epithelial and endothelial cells, and have shown the regulation of Tie-2 by TSH and cAMP in follicular cells. Tie-2 expression is increased in goiter in both humans and rats, consistent with a role in goitrogenesis.

Cell proliferation and apoptosis of thyroid follicular cells are involved in the involution of experimental non-tumoral hyperplastic goiter.

To assess the involvement of cellular inhibition and the appearance of apoptosis in regression of the hyperplastic thyroid gland towards normality, an experimental design was used to elicit non-toxic goiter by inducing hyperplastic goiter in rats by treatment with methimazole. We performed a morphological and PCNA immunocytochemical study together with in situ end labelling with bromodeoxyuridine in thyroid glands of rats receiving methimazole in their drinking water over 21 days after which they were allowed a recovery period of 0, 12, 24, 36, 48 and 72 h and 7, 14, 21 and 44 days. Serum T3 and T4 levels were found to be very low in the methimazole-treated animals although they increased after the goitrogenic compound had been withdrawn. Inhibition of cell proliferation and the burst of apoptosis play important roles in the regression of hyperplastic goiter in rats. Cell proliferation, which was strongly stimulated during goiter, fell significantly at 24 h, thereafter decreasing gradually as the recovery period progressed. Isolated cases of thyrocyte necrosis were observed ultrastructurally. Light and transmission electron microscopy revealed the existence of thyroid apoptosis with respect to the development of the study over time. Most apoptotic thyrocytes became detached from the follicular epithelium and later underwent cellular degeneration in the follicular lumen. The remaining apoptotic cells retracted their cytoplasm, lost contact with the follicular lumen and became located at the base of the follicles. The percentage of apoptosis showed that during the first week of thyroid involution apoptosis was already present but with low percentages while maximum values were attained at 21 days of survival. Our results suggest that, in the rat, during the return of thyroid follicular cells to normality after methimazole-induced hyperplastic goiter a balance arises between proliferation and cell death and that this balance is due to the inhibition of cellular proliferation and, secondarily, to the appearance of apoptosis, which becomes particularly evident towards the end of the first week after withdrawing the goitrogenic agent.

Effects of octreotide on propylotiouracil-induced goiter in rats: a quantitative evaluation.

To evaluate the possible antigoitrogenic effect of somatostatin, the influence of long-acting somatostatin analog--octreotide--on experimental goiter developed in rats treated with propylthiouracil was examined. Goiter formation was assessed by measurement of the main histological compartments of the thyroid as well as by morphometric analysis of the vascularization and blood supply of the gland. Although treatment with octreotide did not prevent the goiter formation, it clearly reduced blood supply and vascularization of the thyroid and counteracted propylthiouracil-induced increase in the relative volume of follicular epithelium. To conclude, the somatostatin analog--octreotide--is effective in reduction of goiter vascularisation. This finding provides a rationale for the clinical trials of the treatment of hypervascular goiter by somatostatin analogs.

Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

The effects of goitrogenesis, involution, and goitrogenic rechallenge on the clonogenic cell content of the rat thyroid.

A fraction of enzymatically monodispersed rat thyrocytes from untreated animals clonally proliferate into thyroid follicular units following transplantation into the subcutaneous fat pads of syngeneic recipients. During the induction of experimental goiters in rats either with 3-amino-1,2,4-triazole/iodine sufficient diet or KClO4/Remington low iodine diet, the clonogenic fractions of cells from aminotriazole goiters decreased to 1.9 x 10(-4) and KClO4 goiters to 9.8 x 10(-5) as compared to 5.8 x 10(-3) for cells from age-matched controls during the growth phase of goitrogenesis. With continued aminotriazole treatment after thyroid hyperplasia had ceased, the clonogenic fraction increased to 2.0 x 10(-3) while continued KClO4 treatment had little further effect. The changes in the clonogenic fraction induced by both regimens were reversed during involution; goitrogenic rechallenge of involuted glands led to changes in the clonogenic fraction similar to that noted during the initial challenge. The clonogenic fractions of cells from aminotriazole goiters were greater than that of cells from KClO4 goiters at all time points examined despite similar TSH levels in situ. We conclude that the rat thyroid contains a hierarchy of cells with different proliferative capacities and that the clonogenic thyrocytes possess many of the attributes of a stem-cell.

Studies on soybean factors which produced goiter in rats.

The goitrogenicities of various preparations obtained from soybean were studied using rats. Thyroid weight, 131I uptake and the ratio of 131I-monoiodotyrosine to 131I-diiodotyrosine of the gland in rats fed the preparation was measured to determine the activity of these preparations. It was resulted that the group of rats receiving the curd had the most hypertrophied thyroid, the enlargement being equal to that in the group of these receiving soybean in the 8 weeks' feeding experiment. No difference on the content of iodine were found with the various diet preparations. The proteolytic digestion of soybean curd did not eliminate the goitrogenic property, thus, the goitrogen seems not to be a protein or peptide-like substance.

Studies on the mechanism of goitrogenic action of diphenylthiohydantoin.

Diphenylthiohydantoin (DPTH) is a potent goitrogenic compound and produces goiters in rats. Like methimazole, DPTH depresses plasma T4 and T3 concentrations and elevates plasma T4 and T3 concentrations and elevates plasma TSH concentration. Unlike methimazole, however, DPTH does not suppress thyroidal radioiodine uptake and thyroid hormone synthesis, although the monoiodotyrosine to diiodotyrosine ration is elevated by DPTH. DPTH does not inhibit thyroidal radioiodine release or augment the degradation of thyroid hormone. DPTH depresses an increase of plasma T4 and T3 in thyroidectomized rats maintained on T4 or T3 by augmenting fecal excretion of hormones. In addition, DPTH decreases conversion of T4 to T3 in vitro. It is suggested that DPTH is a unique goitrogen which acts at two different extrahyroidal sites, viz. fecal loss of thyroid hormone and conversion of T4 to T3.

STUDIES ON THE MECHANISM OF GOITROGENIC ACTION OF DIPHENYLTHIOHYDANTION

Diphenylthiohydantoin (DPTH) is a potent goitrogenic compound and produces a large goiter in rats. Like methimazole, DPTH depresses plasma thyroxine (T4) and triiodothyronine (T3) concentrations and elevates plasma TSH concentration. Unlike methimazole, however, DPTH does not suppress thyroidal radioiodine uptake and thyroid hormone synthesis. DPTH does not depress thyroidal radioiodine release nor augment the degradation of thyroid hormone. DPTH depresses an increase of plasma T3 and T4 in thyroidectomized, T4- and T3-maintained rats by augmenting fecal excretion of hormones. In addition, DPTH depresses peripheral conversion of T4 to T3 in vitro.It is suggested that DPTH is an unique goitrogen which acts on 2 different extrathyroidal sites, viz. fecal loss of thyroid hormone and conversion of T4 to T3.

Species specificity in the TSH response to the administration of L-dopa.

SummaryAcute administration of l-dopa (500-750 mg) lowered plasma TSH concentration and depressed an increase of plasma TSH in response to TRH in patients with primary hypothyroidism. In contrast, chronic administration of small or large doses of l-dopa failed to depress the development of goiter in rats treated with methimazole, indicating that plasma TSH concentration was not lowered by l-dopa in methimazole fed animals. Acute administration of l-dopa also failed to prevent an increase of intrathyroidal colloid droplets produced by an increase of TSH secretion in response to TRH. It is suggested that there is species specificity in the TSH response to the administration of l-dopa.

Effect of fecal loss of thyroxine on pituitary-thyroid feedback control in the rat.

Effects of diets on pituitarythyroid interplay were studied in the rat. Thyroxine, 2 μg ip daily, prevented goiter in rats fed a Remington diet containing propylthiouracil (0.05%). However, when the animals were fed Purina chow with propylthiouracil, 4.5 μg of thyroxine was required to prevent enlargement of the thyroid. Only when 4.5 ng thyroxine was administered did the serum PBI of the Purinafed group reach a value comparable to that of the Remington-fed group, which received 2 μg of thyroxine. Neither the iodine content of the diet nor the thyroxine-plasma protein interaction accounted for this trend of lowered serum PBI. Intestinal absorption of labeled thyroxine was lower in the groups fed Purina than in the group fed the Remington diet, and the serum PB131I of the former group was half that of the latter. The fecal loss of thyroxine was greater in the Purina-fed group than in the Remington-fed group when the animals were fed propylthiouracil and injected with stable and 131I-thyroxine. The serum PB...

Synthesis1 of Ring-Labeled L-Thyroxine-C14

Although I/sup 131/-labeled and carboxyl C/sup 14/-labeled thyroxine have been used to study the metabolism of thyroid hormone, these labels are readily removed physiologically, and knowledge about the metabolic fate of the diphenyl ether moiety of the molecule is incomplete. Preliminary investigation of this aspect of thyroxine metabolism, L -thyroxine labeled with C/sup 14/ in the phenolic ring was synthesized. To utilize a previous method for the convenient preparation of L-thyroxine from p-methoxyphenol, it was necessary to prepare this intermediate from phenol-C/sup 14/ by the reaction scheme which is shown. Then, by modification of the Chalmers method for the condensation of N- acetyl-3,5-dinitroL-tyrosin; ethyl ester with p-methoxyphenol and conversion of the condensation product to L-thyroxine, it was possible to prepare L-thyroxine-C/ sup 14/ in 12 steps in an over-all yield of 2.6%. The detailed procedure is described. The starting material, uniformly labeled C/sup 14/-phenol (specific activity 1.3 mC/mmole, 2.3 mmoles or 216 mg) was converted to phenyl-C/sup 14/- benzenesulfonate by addition of benzensefulfonyl chloride in pyridine. The product was converted to the pnitrophenyl derivative (with KNO/sub 3/ and concentrated H/sub 2/SO/sub 4/ which was converted by alkali to p-nitrophenol-C/ sup 14/. This was treated with diazomethane to form p-nitroanisole-C/sup 14/more » which was reduced with Pt and H/sub 2/ to p-aminoanisole-C/sup 14/. By diazotization p-methoxyphenol-C/sup 14/ was prepared, which was converted to L- thyroxine-C/sup 14/ by the Chalmers procedure. Characterization of the labeled hormone by paper chromatography and assay of its endocrine potency are described. The L-thyroxine-C/sup 14/ exhibited biological activity equivalent to authentic L -thyroxine when tested by the inhibition of propylthiouracil-induced goiters in rats and the suppression of thyroidal I/sup 131/ uptake. (BBB)« less

A Goitrogenic Rat Diet Producing Normal Body Weight Gain.

SummaryBy using 40% of brewers type dry yeast as the principal protein source, a low iodine diet has been designed that supports a good rate of body weight gain and also produces large goiters in rats. This diet appears to have a positive goitrogenic effect, over and above that attributable to its low iodine content.

Thyroxine excretion, a possible cause of goiter.

TWENTY-FIVE years ago McCarrison (1) described an iodide resistant goiter in rats kept under “unsanitary” conditions or fed soy bean meal. A more thorough report was later presented by Sharpless, et al. (2) who showed that rats fed soy meal required two times more dietary iodide to prevent goiter than control rats. It was suggested but not demonstrated that these goiters may have been due to a thiocyanate-type substance in the soy meal. Wilgus, et al. (3) and Halverson, et al. (4) have amply confirmed the goitrogenic action of soy flour. Astwood (5) observed that the goiter in soy-fed rats exhibited a very high 6-hour uptake of I131. This latter observation reduced the likelihood of thiocyanate or propylthiouracil type goiters which, typically prevent retained uptake of I131. At present, all known goitrogenic substances (except thyrotrophic hormone) interfere with thyroid function and cause decreased uptake of I131. Soy bean flour, therefore, must be different since it produced

A Comparison of Triiodothyronine and Thyroxine in the Chick Goiter-Prevention Test

INTRODUCTIONTHE discovery of an unknown iodinated compound as a regular constituent of plasma and thyroid tissue (Gross et al., 1950) led to the discovery of triiodothyronine by Gross and Pitt-Rivers (1952). It has been established that triiodothyronine possesses all of the thyroid hormone qualities of thyroxine when tested in a variety of species (Gross and Pitt-Rivers, 1954). Moreover, triiodothyronine has proven to be from 3 to 7 times more potent than thyroxine in preventing thiouracil-induced thyroid goiter in rats (Gross and Pitt-Rivers, 1953; Tomich and Wollett, 1954). Since the above studies have been largely restricted to mammals, it seemed of some interest to determine the potency of triiodothyronine in terms of thyroxine in the fowl by means of the goiter prevention test.MATERIALS AND METHODSExperiments were performed on Single Comb White Leghorn cockerels maintained on commercial laboratory chow (containing 5 ppm. iodide) and caged under 24-hour infra-red illumination… .

The effect of low iodine diet on thyroid function in the rat.

IT HAS long been known that normal thyroid function is dependent upon an adequate intake of dietary iodine. In more recent years many studies have been made in an attempt to elucidate the exact role iodine plays in the development and function of the thyroid gland. The vast amount of data obtained on this subject has been amply discussed in many textbooks and review articles and will not be considered in detail in this report. In rats, as in most other vertebrates, thyroid changes develop when the dietary level of iodine is low. A deficiency in iodine intake produces a decrease in the synthesis of thyroid hormone and results in the formation of an hyperplastic goiter. The administration of iodine under such circumstances corrects this deficiency, and the gland assumes a more normal structure. In 1933 Levine, Remington and Von Kolnitz (1, 2) developed a low iodine diet which produced goiter in rats within five weeks. By the use of this diet and with replacement of iodine with potassium iodide, they conclud...