Low Iodine Diet Research Articles

Paradoxical stimulation of thyroid function by cortisone in the rat.

We have studied the effect of cortisone on 131I metabolism of highly stimulated rat thyroids. Rats were fed a low-iodine diet (LID) containing 0.15% propylthiouracil (PTU) for 7 days. The PTU diet was withdrawn on day S and LID alone fed for another 4 days. Half of the animals received 5 mg cortisone daily from day 6 to the day of autopsy. The 4-hr thyroid 131I uptake was consistently higher in the cortisone-treated rats than in the controls after PTU withdrawal. Similar differences between cortisone and control groups were seen in acutely nephrectomized rats and in those hypophysectomized and maintained with TSH. Higher T3*/T4* and MIT*/DIT* ratios were found in the digested thyroids of the intact cortisonetreated rats than in the controls. The T/S (TcO4–) was significantly higher in cortisonetreated animals than in controls. A single injection of cortisone did not affect the 4-hr thyroid 131I uptake in PTU-withdrawal rats, but decreased the 12 and 24-hr 131I accumulation. The increase in thyroid 131I me...

Effects of 3-nitro-L-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect.

The effects on thyroid function of an inhibitor of tyrosine dehalogenase, 3-nitro-L-tyrosine (MNT) have been investigated in rats. In preliminary studies, marked inhibition of iodotyrosine deiodination was demonstrated in rats drinking 8 mM MNT. A series of experiments was then performed in which rats received Remington low iodine diet and 8 mM MNT as drinking fluid. This regimen had the following effects, compared to the effects of a low iodine diet alone: (a) a decrease in serum protein-bound iodine, elevation of serum thyrotropin level, goiter, and growth inhibition all prevented or reversed by iodine supplements: (b) on initiation of MNT, a 2- to 3-fold increase in the rate of release of radioiodine from the thyroid and concomitant urinary excretion of large amounts of organic iodine: and (c) after 2 wk of MNT, a greatly increased rate of thyroidal uptake and release of (131)I, an increase in the ratio of monoiodotyrosine-(131)I to diiodotyrosine-(131)I in thyroid proteolysates and the appearance of labeled iodotyrosines in serum. Acute administration of MNT intraperitoneally to rats on either an iodine-deficient or iodine-sufficient diet did not inhibit thyroidal uptake of (131)I or alter the distribution of (131)I among thyroidal iodoamino acids. It is concluded that MNT is an effective inhibitor of iodotyrosine deiodination in vivo, without other important actions on thyroid function. Thus, MNT treatment affords a model for the human dehalogenase defect. By provoking iodotyrosine secretion and consequent urinary loss of iodine, MNT can exaggerate the effects of a low iodine intake, producing goitrous hypothyroidism despite a rapid rate of iodine turnover in the thyroid.

Experimental procedures leading to a relative accumulation of non-thyroglobulin thyroidal iodocompounds in rat thyroid glands.

ABSTRACT A small amount (3–4 per cent) of the homogenate of normal rat thyroid glands, labelled with radioiodine, resists enzymatic digestion by pancreatin and pronase and remains at the origin in alkaline and acid paper chromatography (»origin material«). Under certain conditions the pancreatin resistant compound can account for over 50 per cent of intrathyroidal iodine. The percentage of labelled origin material increases when the interval between single shot labelling and enzymatic digestion of the gland is extended to several days or weeks. The phenomenon is even more pronounced when the rats are kept on a low iodine diet (LID) during the whole experiment. Furthermore a relative increase of the labelled iodinated material occurs when rat thyroid glands are blocked with a thyrostatic drug or labelled to near isotopic equilibrium instead of short term labelling only. If the rats are kept on LID during the equilibration procedure, the relative concentration of origin material will again exceed that found in the thyroids of the control rats kept on HID. Autoradiography revealed that the centre of a PTU-blocked thyroid gland contains little radioactivity whereas large amounts of labelled colloid remain in the peripheral follicles. Mechanical separation of the peripheral layers from the thyroid core indicates that the enzyme resistant material is located mainly in hypcrplastic follicles. Ultracentrifugation studies have shown that the substance is heterogeneous. A small fraction is sedimented at low centrifugal speed, the bulk, however, remains in the supernatant and is of low molecular weight as shown by sucrose density centrifugation and sephadex gel filtration.

Failure of dinitrotyrosine to affect the TSH-induced acute depression of thyroidal iodide transport.

Dinitrotyrosine (DNT), a potent inhibitor of thyroid iodotyrosine deiodinase, failed to affect the acute TSH-induced depression of the thyroid-.serum radioiodide concentration [T/S(I~)]. This finding lends support to the concept that the acute TSH-induced depression of T/S(I~) is not caused by expansion of the intrathyroidal iodide pool consequent upon increased proteolysis of thyroglobulin and deiodination of free iodotyrosines following TSH administration. (Endocrinology 88:1277,1971) T (TSH)-induced release of iodide from thyroids was reported by Becker et al. (1) in 1953 and other groups (2). Halmi et al. (3) described a biphasic effect of TSH on thyroid iodide concentration in the rat with an early depression of the thyroid: serum radioiodide ratio [T/S(I~)], 4-5 hr after injection of TSH, followed by a later rise which exceeded the pre-TSH levels. The early depression was explained by them as due to an increased exit rate for iodide (4). Rosenberg (2) and Wolff (5) considered TSH-induced hydrolysis of thyroglobulin with subsequent deiodination of iodotyrosines and expansion of the thyroid iodide pool as another possible cause. However, studies (3) in iodine-deprived rats whose thyroid glands would contain relatively small amounts of iodotyrosines showed a TSHinduced early depression of the T/S(I~), similar to that of animals not deprived of iodine. In the present experiments, the problem has been explored further by inhibiting deiodination of free intrathyroidal iodotyrosines by administration of dinitrotyrosine (DNT). Materials and Methods Experiments with in situ perfusion. To demonstrate the inhibitory effect of DNT administered in vivo on intrathyroidal deiodination of iodotyrosines, male Sprague-Dawley rats weighing 200-300 g were fed Purina laboratory chow or a low iodine diet (approximately 30 Mg I/kg, General BioReceived February 26, 1970. This investigation was supported by Grants AM-01447 and AM-05065 from the National Institute of Arthritis and Metabolic Diseases, NIH. The work was completed with support from Grant 36X0161, Medical Research VA, 1970. 1 Trainee in Endocrinology of the National Institute of Arthritis and Metabolic Diseases. Present address: Veterans Administration Hospital, Jefferson Barracks Division, St. Louis, Mo. 63125. chemicals, Inc., Chagrin Falls, Ohio). They were injected with carrier-free I~ 16—24 hr and with DNT 105-120 min before exsanguination. Sufficient I was injected ip to obtain a thyroid content of 30-60 /uCi at the time of perfusion. DNT was prepared as described below and injected sc in the doses shown in Table 1. Immediately after sacrifice, the thyroid glands were perfused in situ by the technique developed in this laboratory (6). The entering perfusate contained bovine thyrotropin (TSH) (a gift of the National Institute of Health, lot NIH-B4), 1 U/100 ml, to maintain thyroid secretion. The total radioactivity secreted per min and the relative distribution of labeled compounds did not appreciably change over the first 30 min of perfusion when TSH was added to the perfusate (6). The perfusion lasted 30-45 min. Two or 3 thyroid effluent collections were made. Only the last one is presented in Table 1. Thyroid effluent plasma, pancreatin digests of the glands removed after perfusion, and the plasma obtained during exsanguination before perfusion were analyzed by paper chromatography in butanol-ethanol-ammonia (BEA) or butanol-acetic acid-water (BAW) systems to determine the relative quantitative distribution of labeled iodoamino acids and iodide (6). Origin material was not included in the calculation of the relative distribution. The degree of inhibition of iodotyrosine deiodination was estimated by comparison of the per cent of labeled MIT and DIT in the effluent with that in the thyroid digest. The mean effluent percentage iodotyrosines of all DNT-treated rats in Table 1 (57.3+1.8 SEM) was divided by that of the digest (68.9+2.1 SEM), which was 83%. It was assumed that the inhibition is complete when the percentage iodotyrosines secreted equals that of the digested thyroglobulin. Greer and Grimm (7) achieved almost complete inhibition by this criterion when they perfused prelabeled thyroids with blood containing 10~ and 10~M DNT. Experiments involving T/S(I~) ratios. Male Sprague-Dawley rats weighing 120-150 g were fed Purina chow and given tap water ad lib. TSH was obtained from the Armour Pharmaceutical Co.,

The importance of the ionic strength of sucrose gradients in the determination of the sedimentation coefficient of poorly iodinated or newly synthesized thyroglobulin

The sedimentation rate of thyroglobulin from iodine-sufficient or iodine-deficient rats was examined in sucrose gradients prepared in buffers of different ionic strengths at pH 6.8. Iodine deficiency was obtained by feeding rats a low iodine diet for 15–18 weeks, alone or with addition of NaClO 4 or propylthiouracil for 7 days. The poorly iodinated in vivo 125I-labeled or in vitro 14C-labeled thyroglobulins sedimented in a symmetrical approx. 18-S peak in sucrose gradients made in phosphate-NaCl buffer with ionic strength of 0.40 and similarly in the same buffer with ionic strength of 0.15 for less poorly iodinated thyroglobulin. In sucrose gradients made in 0.01 M phosphate buffer all thyroglobulins with an iodine content lower than 0.1% showed heterogeneity. This consisted in the appearance of a new 14–16-S species, the amount of which was inversely related to thyroglobulin iodine content and which was likely an unfolded form of approx. 18 S. Unfolding of the approx. 18-S into the 14–16-S species was partially reversible. The unfolded 14–16-S form was easily dissociated into approx. 12-S subunits. The results indicated that dissociation of thyroglobulin into subunits is probably preceded by unfolding of the molecule. Low sedimentation coefficients of poorly iodinated thyroglobulins reported by several investigators are related to environmental factors such as the ionic strength of the buffer at a near neutral pH used to make the sucrose gradients.

Thyroid function of genetically obese rats.

Radioactive iodine was released from the thyroid of genetically obese rats more slowly than from glands of lean or lesioned-obese rats. The uptake of radioiodine was also less in the genetically obese rats fed a low iodine diet, but not when the intake was high in iodine. Administration of exogenous TSH produced similar rates of release of radioactive iodine from the thyroids of lean and obese rats. The possibility of hypothalamic dysfunction in the genetically obese fatty rat was discussed. (Endocrinology 88: 1095, 1971) I 1961, Zucker and Zucker reported a strain of rats in which obesity is inherited as a mendelian recessive trait (1). Among the several defects which have been described in these rats (2) were hyperlipemia (3, 4) and a reduction in oxygen consumption (5). This latter observation led to the present studies of thyroid function of these animals. Materials and Methods Animals. Nineteen genetically obese female rats, 9 control obese rats and 16 lean female rats were used for these studies. Obesity developed in control rats following the introduction of bilateral electrolytic lesions of the hypothalamus, as described previously (6). All rats were maintained on Purina Laboratory Chow or on a low iodine diet (7) with tap water available ad lib. Procedures. Five experiments were performed. In the first experiment, 6 genetically obese rats and 6 lean litter mates were fed a low iodine diet for 14 days. Approximately 10 /*Ci of I was injected 24 hr before the experiment. Radioactivity remaining in the thyroid was assayed twice daily by placing the neck over a collimated well-type scintillation counter and recording 4000-10,000 counts. During the experiment, recycling of iodine was blocked by adding potassium perchlorate (1% w/v) to the drinking water. For the second experiment, 9 genetically obese, 6 lean and 5 lesioned rats were fed 14 g of food daily. Radioactive iodine uptake was determined twice, once on the chow diet and again after feeding a low iodine diet for 10 days. In the third experiment, 5 genetically obese and 5 lean litter mates were used. Twenty-four hr after injection of I, potassium perchlorate (1% w/v) Received May 11, 1970. Supported in part by Grants AM-9897 and AM05166 from the NIH. Reprint requests to: Dr. George Bray, 1000 W. Carson St., Torrance, Calif. 90509. 1 Genetic obese rats obtained from Dr. L. M. Zucker, Harriet G. Bird Memorial Laboratory, Stow, Mass. was added to the drinking water and each rat was started on a daily injection of 7.5 ng of thyroxine. After 4 daily neck counts, injections of thyrotropin, 300 mU/100 g/day, were given along with the thyroxine for an additional 4 days. The fourth experiment was performed on 4 genetically obese and 4 lesioned-obese rats fed chow diet. Measurements of uptake and release of I were performed as described for the first experiment. The fifth and final experiment utilized the same rats as the second experiment. A low iodine diet was fed ad lib. for 10 days. Twenty-four hr before sacrifice, each rat received 25 /xCi of I ip. Samples of blood were obtained from the abdominal aorta. The thyroid gland was dissected free, weighed, and the radioactivity measured with a well counter. Half of the thyroid was used for determination of total chemical iodine and the other half was homogenized and incubated with pronase overnight at 37 C. Aliquots of this digest were applied to strips of No. 3 Whatman filter paper and chromatographed in 2 systems (8). The strips were dried and the appropriate spots cut out and counted in a gamma counter. I-PBI was measured on § ml of the serum after 3 washes with 3 ml 10% TCA. The precipitate was then analyzed for PBI. Materials. Thyrotropin (Thytropar, Armour and Co., Chicago, 111.) was diluted in 0.15M saline. Thyroxine (Sigma, St. Louis, Mo.) was dissolved in 0.5N NaOH and then diluted in 0.15M saline. The low iodine diet (7) was purchased from Nutritional Biochemicals Co., Cleveland, Ohio. Calculations. Data are expressed as mean±SE. Analysis of variance, regression lines and correlation coefficients were determined using a desk top calculator.

Prompt stimulation by TSH of thyroid oxidation of thiocyanate.

TSH (4 U, iv)1 was given to rats on a low iodine diet 30 min before an ip injection of KSCN labeled with 35S; within 15 min after the SCN injection, thyroid oxidation of thiocyanate was significantly greater than in controls not given TSH. Prompt stimulation of thyroid oxidation of SCN was also observed in Purinafed rats, including animals acutely pretreated with perchlorate. The formation of sulfate by calf thyroid slices incubated in 0.1 mil KSCN was enhanced within 15 min by TSH (50 mU/ ml). In canine thyroid slices, supplementing the medium with dbcAMP also stimulated thiocyanate oxidation. Thiocyanate oxidation by bovine thyroid slices was enhanced by the presence of 0.1 mM H2O2 or a hydrogen peroxide generating system in the medium. Both basal and TSH stimulated oxidation of SCN were inhibited by methimazole, thiols, anaerobiosis and inhibitors of electron transport. The promptness with which TSH augments thyroid oxidation of thiocyanate, as well as other features of this response in vivo and in vit...

Thyroid hydrolysis of cyclic AMP as influenced by thyroid gland activity

1. 1. Cyclic AMP phosphodiesterase activity in rat thyroid homogenates was studied. Enzyme activity was maximal at pH 7.5–8.0 and was entirely localized to the 100 000 × g supernatant fluid. 2. 2. The apparent K m for cyclic AMP in whole homogenates and in the 100 000 × g supernatant fluid was 0.3–0.5 mM. 3. 3. Chronic thyroid stimulation, produced by feeding a low-iodine diet or 6- n-propylthiouracil, increased enzyme activity and thyroid suppression produced by adding thyroid U.S.P. to the diet, depressed the activity. 4. 4. 10 mM theophylline in the reaction mixture greatly inhibited cyclic AMP hydrolysis, but the same relative changes persisted. 5. 5. Phosphodiesterase activity, measured 15 min and 2 and 12 h after a single intravenous injection of 200 mU thyrotropin, was unchanged. 6. 6. It is suggested that hydrolysis of the high-energy 3′-bond of cyclic AMP may be related to its actions in mediating the effects of thyrotropin. 7. In addition to inhibiting cyclic AMP hydrolysis, theophylline is also a 5′-nucleotidase inhibitor. The major products of cyclic AMP hydrolysis were dephosphorylated compounds, but in the presence of theophylline, appreciable amounts of AMP accumulated. When AMP was used as substrate, theophylline inhibited its hydrolysis.

Changes of the radioactive iodine uptake and in the iodoamino acids pattern of thyroid in rats in the course of advancement of iodine deficiency.

Hourly changes of 131I uptake and the changes in several indices of thyroid at different time intervals after beginning of an iodine deficient diet with or without propylthiouracil were determined. An amino acid mixture was used as the protein source in the present experiments. The magnitude of iodine uptake and the ratio of monoiodotyrosine to diiodotyrosine increased according to the length of time on low iodine diet. The earlier appearance and more enlargement of peak of the ratio of monoiodotyrosine to diiodotyrosine in rats treated with small dose of propylthiouracil than in those untreated suggested that propylthiouracil might also bring about the lack of iodine by inhibiting the iodination at substrate level.

Differences in composition and function of iodinated substances in stimulated thyroid glands

Rats were fed a low-iodine diet for 18 months and this was labeled with 125I for the last 6 months. Their thyroids rapidly approached isotopic equilibriu for 10 days but they showed a slow increase in radioiodide for 4 months after 125I was begun. The slowly accumulated radio-iodine was slowly released but ultimately it had labeled 71 per cent of the total iodine in the gland. Approximately 23 per cent of the thyroidal iodine was labeled rapidly by an acute tracer dose of 131I, this component probably supplied the day by day requirements of iodinated proteins. There was little thyroid hormone in the iodinated proteins such that the daily hormone secretion rate of the gland was 4–5 times greater than the total hormonal iodine in the glands. It is suggested that the daily hormone requirement was supplied by such a small part of the thyroidal iodine that the rapidly labeled thyroglobulin pool required replacement more than 13 times each day. The animals appeared euthyroid but their PBI was less than 0.3 μg. per cent. In similar animals given a single dose of 125I, the radioiodine was depleted by continuing low-iodine diet and feeding potassium perchlorate for 10–14 days. The residual thyroidal radioiodine was slowly released and this was separated into soluble (27%) and insoluble (73%) fractions. The soluble iodinated material had many characteristics suggestive of an iodinated nucleotide.

In vitro influence of thyrotropin or long-acting thyroid stimulator on mouse thyroid membrane potential

The few data available indicate that resting membrane potential (MP) of thyroid acinar cells is reduced in animals given thyrotropin or goitrogen in vivo. There-fore we measured MP in mouse thyroids in vitro with and without thyrotropin in the superfusate and studied the effects of LATS-IgG. Potential was measured by use of glass micro-electrodes that had a tip resistance of 15–35 MΩ and a tip diameter of less than 1 μ. Intracellular potential was −39.1 mV ± 0.3 (SD) for 423 measurements; potential was linearly less negative with increasing log [K +], approximately 23 mV per ten-fold change in [K +]. There was depolarization with lowering of temperature or superfusion with 10 −4 ouabain or 5 × 10 −4 M dinitrophenol and in thyroids from mice given low-iodine diet for nine days. Superfusion with thyrotropin of glands with iodine labelled with 125I resulted in enhanced release of TCA-soluble radioactivity. Similar glands showed a reduced MP in response to superfusion with either thyrotropin (10 mU./ml.) or LATS-IgG solutions, there being no effect of solvent (1% human serum albumin) or normal human IgG. The effects of both thyrotropin and LATS-IgG appeared promptly and the potential returned to normal in both instances within 10 minutes of changing to control superfusing buffer. Conclusions are that depolarization of thyroid cell membrane is a prompt in vitro response to either thyrotropin or LATS; repolarization occurs rapidly after removal of the stimulators, indicating no persistence of the effect of LATS, relative to that of thyrotropin.

Further studies on the 27S and 32S optical density peaks of the rat thyroid.

ABSTRACT In this paper evidence is presented that a 27S Optical Density (O. D.) peak is absent and a 32S O. D. peak is regularly present on analysis of the soluble thyroid proteins of the goitrous rat. This occurs irrespective of the goitrogenic stimulus and a normal O. D. pattern can be restored by reversal of the goitrous process by thyroxine. In rats rendered goitrous by a low iodine diet or KClO4 treatment, iodine supplementation also removed the 32S O. D. peak and resulted in reformation of the 27S peak. In rats treated by antithyroid drugs of the thiocarbamide group loss of the 32S O. D. peak was not associated with recovery of a 27S peak. This may be related to differences in potency of the various antithyroid drugs. 125I and 3H-leucine were not incorporated into the 32S O. D. peak material of the rat thyroid in vivo or into the 32S O. D. peak material of sheep thyroid slices in vitro. The view that this 32S O. D. peak was not iodoprotein nature was confirmed by showing that this peak had a maximal absorbance at 260 nm favouring the hypothesis that it was composed of nucleic acid.

Antithyroid effects of lithium.

Lithium has been reported to be goitrogenic when used for the treatment of manic-depressive psychosis. To investigate the effects of lithium on iodine metabolism, male Sprague-Dawley rats were placed on a low iodine (LID) or normal iodine diet (NID) containing enough Li(2)CO(3) to give serum lithium levels of 0.23-0.86 mEq/liter (human therapeutic range is 0.6-1.6 mEq/liter). The following effects were noted with lithium treatment: (a) thyroid weight increased concomitant with a slowing of thyroidal iodine release; (b) the ability to concentrate iodide was increased only after goiters were established; (c) on the LID, (131)I uptake was elevated throughout all phases of treatment, even when the release rate was normal; (d) iodine organification was unaffected but the proportion of (131)I present as iodothyronines was decreased; (e) the thyroidal (127)I content was increased; (f) despite these changes, the serum PBI remained normal as did the thyroxine turnover rate; and (g) thyrotropin (TSH) levels in serum were the same as controls except for a slight elevation early in the course of treatment; TSH levels did not correlate with goitrogenesis. When LiCl was injected in large doses into intact rats (giving serum lithium levels of 3.08-3.89 mEq/liter), the iodide concentrating mechanism, (131)I uptake, and (131)I release rates were depressed. Similar experiments in hypophysectomized rats receiving TSH demonstrated these to be local antithyroid effects not mediated through the pituitary. The discrepancy between acute and chronic responses to lithium, and the dissociation between the inhibition of iodine release and stimulatory effects is discussed.

Low dietary iodine intake and the functional activity of the rat thyroid.

SummaryThe effects of low dietary iodine intake on the functional activity of the thyroid were studied in young female albino rats. The low iodine diet contained 0.05 ppm iodine, with casein as the primary protein source. Feeding this diet to 30-day-old rats for periods of up to 3 months increased the thyroid hormone secretion rate (TSR). The FBI was within the normal range but thyroid size was slightly increased as compared to the corresponding control rats of the same age fed Purina Lab Chow. On the low iodine diet, the percentage uptake of thyroidal-133I was greatly increased, and the biological half-life of thyroidal-131I was significantly reduced, indicating a faster turnover of thyroidal-iodine (hormones). The DNA content of the thyroids indicated hyperplasia and hypertrophy suggesting stimulation of the gland. It was concluded that under these experimental conditions the rat thyroid has the capacity to increase its activity to compensate for any moderate low dietary iodine for at least 3 months by ...

Micropuncture investigation of the effect of altered thyroid function on the cation concentrations and equilibrium potentials in rat thyroid colloid.

By means of micropuncture of single rat thyroid follicles, the cation composition of colloid was studied in normal adult and weanling rats, in rats reared on high and low iodine diets and in rats traated with thyroxine or thyroxine plus potassium perchlorate. The diets had no effect on the distribution of sodium between plasma and colloid but there were marked effects on potassium distribution. Both high and low iodide diets caused the potassium equilibrium potential difference between colloid and plasma to be increased whereas immaturity, and treatment with thyroxine alone or thyroxine plus perchlorate caused it to decrease.

Studies on the antithyroid activity of naturally occurring L-5-vinyl-2-thiooxazolidone and its urinary metabolite in rats.

ABSTRACT Rats were force fed a single dose of 20, 40, 80, 160, 320, 640, 1280 and 2560 μg L-5-vinyl-2-thiooxazolidone (VTO) and injected with 131I one hour later. The 131I uptake, biosynthesis of thyroid hormones and PB131I were measured 4 h after the administration of 131I. Under these conditions, a higher antithyroidal effect with VTO was found in rats fed a normal diet (ND) for 10 days before the experiment as compared with rats fed a low iodinediet (LID) for the same period. The results are described in detail. Similar doses of VTO were force fed to groups of rats fed LID daily for 20 days. The animals received 1 μCi 125I per 15 ml of drinking water for 30 days before sacrifice. One hour after the last dose of VTO they were injected with μCi 131I and killed 4 h later. In addition to the parameters presented above the thyroid weight, total 125I in the thyroid and PB125I were measured. The inhibition of thyroid activity was in direct relation to the dose of VTO administered. Finally, ethereal extracts of urine of rats kept in metabolic cages and force fed a single dose of 10 mg VTO were prepared and the dried extract was dissolved in methanol and applied to the chromatographic paper. In two chromatographic systems (1. water saturated chloroform, 2. n-butanol:acetic acid:water) two compounds were detected, one of which (Compound A) was chromatographically identical with VTO and the other (Compound B) was unknown. The Compound B was extracted from chromatograms, its UV-absorption spectrum was measured and its antithyroid activity was tested in rats. The 131I uptake was significantly inhibited following a single administration of 640 μg Compound B.

The methyl xanthines--a new class of goitrogens.

Rats chronically fed methyl xanthines in a low iodine diet developed goiters. The potency of the compounds tested was in the order: theophylline =aminophylline> caffeine > theobromine. Goitrogenesis was reduced on high iodine diets and absent in hypophysectomized rats. Theophylline caused marked, synergistic enhancement of the goitrogenic effect of small doses of propylthiouracil. Aminophylline and theophylline lowered the PBI but at theophylline concentrations prevailing in these sera little antithyroid activity could be demonstrated in rat thyroid segments in vitro. It is concluded that the methyl xanthines are mildly antithyroid and strongly goitrogenic compounds. The possibility that this dissociation between the antithyroid and goitrogenic response involves mediation by 3′,5′-AMP is discussed. (Endocrinology 85: 410,1969)

Thyroglobulin biosynthesis in severely iodine-deficient rats.

SUMMARY Studies of the in-vivo biosynthesis of thyroglobulin in rats on a low iodine diet have been extended to produce more severe degrees of goitre formation. In this situation the protein in the thyroglobulin region did not become less than 18S and both 125I and [3H]leucine were rapidly incorporated into this protein. These results confirm and extend previous observations.

Dependence of protein-binding of iodide on concentration of thyroidal iodide in chickens.

Chickens which had been fed either a control or low-iodine diet were injected with graded doses of stable iodide; concentrations of serum iodide and newly entered thyroidal iodide and protein-bound iodine were measured at the end of 1 hr. T/S[I-], ratio of the concentration of iodide in the thyroid to that in an equivalent amount of serum, was initially independent of concentration of serum iodide as the latter was increased from low levels, then increased by a factor of 15–25, and finally declined to a value of <1. The concentration of proteinbound iodine increased progressively as thyroidal iodide increased; a minor, statistically significant decrease (Wolff-Chaikoff effect) occurred at relatively high levels of thyroidal iodide in birds fed the low-iodine diet but not in the control birds. (Endocrinology 85:231,1969)

Stimulation of thyroid hyperplasia and protein synthesis by LATS.

The effect of LATS on protein synthesis in the mouse thyroid in vivo was compared to the action of TSH. A single injection of LATS or TSH in a thyroxine pretreated mouse failed to stimulate the incorporation of 3H-leucine into thyroidal protein. Injection of LATS for 5 days caused increased thyroid weight, augmented protein content, and increased incorporation of 3H-leucine. The specific activity of incorporated radioactivity per mg thyroid protein was significantly increased. Feeding a low iodine diet for 12 days increased incorporation of radioactivity and specific activity. Treatment with LATS or TSH for 8 days produced marked goiter formation accompanied by a high 131I thyroidal uptake. LATS stimulates protein synthesis in the thyroid, as does TSH. LATS does not appear to damage the thyroid cell since chronic exposure leads to marked goiter formation. (Endocrinology 85:344,1969)