Down regulation of hypertrophied follicular cell volume in thyroid hyperplastic gland

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.     

Negative Effect of Iodide On the Survival of Newly Divided Epithelial Cells In Chronically Stimulated Rat Thyroid

Abstract. The aim of this work was to investigate some aspects of the thyroid epithelial cell kinetics during the iodide-induced involution of a hyperplastic goitre in the rat. Rats were made iodine-deficient for 6 months, and propylthiouracil (PTU) (0.15%) was added to the diet during the last 2 months. Thereafter, rats were refed with iodide and PTU was removed (day 0).
Forty-eight hours previously, all the rats were injected with tritiated thymidine ([³H]TdR) (1 μCi/g). Some animals were killed 1 hr or 24 hr after [³H]TdR injection (i.e. on day -2 and -1, day O corresponding to the restoration of a normal iodine diet); the other animals were killed after different delay periods and following L³H]TdR injection. Autoradiography of thyroid sections, iodine determination of plasma iodide and protein-bound iodine (PBI), and RIA of plasma thyroid stimulatory hormone (TSH) were performed. Plasma TSH concentration was very high on day O of iodide refeeding (3000 ± 330 ng/ml) and remained at this level until day 8. Plasma PBI was very low on day O, remained so until day 4 and greatly increased on day 8. Plasma iodide was also very low on day O, but markedly increased on day 1, then did not vary significantly until day 43 of iodine refeeding. Thyroid weight, elevated on day O, decreased relatively quickly until day 30, then more slowly until day 73.     

Negative effect of iodide on the survival of newly divided epithelial cells in chronically stimulated rat thyroid

The aim of this work was to investigate some aspects of the thyroid epithelial cell kinetics during the iodide-induced involution of a hyperplastic goitre in the rat. Rats were made iodine-deficient for 6 months, and propylthiouracil (PTU) (0.15%) was added to the diet during the last 2 months. Thereafter, rats were refed with iodide and PTU was removed (day 0). Forty-eight hours previously, all the rats were injected with tritiated thymidine ([3H]TdR) (1 microCi/g). Some animals were killed 1 hr or 24 hr after [3H]TdR injection (i.e. on day -2 and -1, day 0 corresponding to the restoration of a normal iodine diet); the other animals were killed after different delay periods and following [3H]TdR injection. Autoradiography of thyroid sections, iodine determination of plasma iodide and protein-bound iodine (PBI), and RIA of plasma thyroid stimulatory hormone (TSH) were performed. Plasma TSH concentration was very high on day 0 of iodide refeeding (3000 +/- 330 ng/ml) and remained at this level until day 8. Plasma PBI was very low on day 0, remained so until day 4 and greatly increased on day 8. Plasma iodide was also very low on day 0, but markedly increased on day 1, then did not vary significantly until day 43 of iodine refeeding. Thyroid weight, elevated on day 0, decreased relatively quickly until day 30, then more slowly until day 73. The [3H]TdR labelling index (LI) of the thyroid epithelial cells (TEC) was high on day 0 (56 +/- 3 labelled cells/10,000 cells), and 24 hr thereafter increased to 104 +/- 3, by division of the labelled cells. On day 1 of iodine refeeding, the LI had abruptly decreased to about half this value and then remained stable for 3 more days. Between day 4 and day 16, a progressive decline in the LI, (by about 3-4 per day), was observed. The LI showed no further modification, up to day 73, the longest period investigated. The decrease in LI occurred without any significant changes in the labelling intensity (grain count) of the remaining labelled cells between day 1 and 16, this indicates that no cell division took place during this period. The data are therefore interpreted as showing a biphasic elimination after iodide refeeding, of cells that were actively proliferating during the goitrous state.(ABSTRACT TRUNCATED AT 400 WORDS)     

Possible regulation of the growth of thyroid tissue by plasma iodide

Rats on iodine deficient diet for 6 months received propylthiouracil (PTU) (0.15%) during the last 2 months. At the end of this treatment, PTU was withdrawn and the rats were iodine refed. 48 hrs. before the iodine refeeding all rats were injected with 3H thymidine. The results showed that some prelabelled cells in the hyperplastic goitre preferentially disappeared during its involution and therefore are more sensitive to iodine.     

Fine structural aspects of the black thyroid induced by minocycline, and the effects of a low iodine diet, propylthiouracil, thyroxine tablet and TSH, on the black discoloration of the rat thyroid

Fine structural aspects of the effect of minocycline, an antibiotic of the tetracycline group, on the rat thyroid were studied. In all the rats administered minocycline (100 mg/kg/day) for 21 days, diffuse black discoloration of the thyroid gland occurred. However, when the rats were fed on a low iodine diet, given propylthiouracil (PTU) or thyroxine tablet with minocycline the black pigmentation of the thyroid gland did not take place. On the other hand, black discoloration of the thyroid was accelerated in the rats administered TSH and minocycline simultaneously. Ultrastructurally, numerous dense bodies containing highly electron-dense deposits were seen in the supranuclear region of the follicular epithelial cells of the black thyroid. These dense bodies, which showed positive acid phosphatase activity, are considered to be lysosomes containing minocycline or its derivatives. It is speculated that minocycline is taken up into follicular epithelial cells with iodine, and that the black discoloration of the thyroid gland is intimately related to iodine metabolism.     

Ultrastructural changes in thyroid epithelium during involution of the hyperplastic thyroid gland

The ultrastructure of the thyroid epithelial cell was examined at various time intervals after induction of involution of the hyperplastic thyroid gland. Thyroids were made hyperplastic by the feeding of thiouracil in a Remington low-iodine diet to male Fischer rats for 3 weeks. Involution was induced by replacing the thiouracil-containing diet with Purina Laboratory Chow, a high-iodine diet. During involution, organelles that play a role in the synthesis and secretion of thyroglobulin, such as the rough endoplasmic reticulum, Golgi apparatus, and apical vesicles, were well preserved and prominent features of the epithelial cell. The apical plasma membrane of many cells was highly irregular for approximately 2 weeks with signs suggesting rapid discharge of apical-vesical contents into the lumen of the follicle. Pseudopods and colloid droplets were present but were not very prominent features of the cell. No signs of extensive autophagy or obvious increased incidence of lysosomes were present, although there was an elevation in the incidence of small dense bodies starting about day 8, and prominent by 15 days. Some of these may be phagosomes formed from luminal debris. The observations indicate that involution of the hyperplastic thyroid in which there is maintenance of the protein synthetic apparatus and little sign of autophagy or death of the epithelial cells is remarkably different from phenomena occurring during involution of prostate or mammary glands.     

Effects of thyroidectomy and administration of propylthiouracil (PTU) or thyrotropin (TSH) to pregnant rats on the functional development of the fetal thyroid gland an immunohistochemical study

In order to elucidate the maternal factors influencing the functional development of the fetal rat thyroid gland, pregnant rats were subjected to either thyroidectomy or administration of PTU or TSH and the thyroid glands of the fetuses were examined chronologically by immunohistochemistry to detect thyroglobulin (Tg), T4 and T3. In the group undergoing thyroidectomy, the occurrence of immunoreactive Tg, T4 and T3 was the same as in the control group in spite of slight retardation of the development of the thyroid gland. On the other hand, PTU administration caused remarkable degeneration of the hyperplastic epithelium of the follicles, where immunoreactivity of T4 and T3 was barely detectable, suggesting a transplacental effect of PTU on the fetal thyroid gland. However, Tg remained unaffected and was stained as well as in the controls. Injection of TSH led to a delay in the occurrence of T4 and T3 by one day, probably due to increased levels of thyroid hormone from the stimulated thyroid gland of the mother rats.     

Therapy of endemic goitre: controlled study on the effect of iodine and thyroxine

Two kinds of medical treatment of endemic goitre (400 microgram of iodine, n=11, and 150 microgram of L-thyroxine, n=12) were compared in a double blind study with a placebo group (n=12) during a period of 12 months and an observation time of three months after cessation of therapy. The means of the neck circumference and of the estimated thyroid volume decreased significantly during treatment in both groups, whereas no significant difference was observed in the placebo group. The results in both therapy groups did not differ significantly from each other. No side effects or symptoms of hyperthyroidism were observed. During treatment the index of free thyroxine (FT4I) increased significantly in both the iodine and the thyroxine group and delta TSH after TRH decreased significantly. Total triiodothyronine (TT3) did not show significant alterations. Three months after cessation of therapy in the thyroxine treated group the mean FT4I dropped into the range before treatment, whereas it remained slightly elevated in the iodine group. In the thyroxine treated group the mean delta TSH was higher than its value before therapy. After withdrawal of iodine, however, the mean delta TSH remained decreased for three months. The study indicates that 400 micrograms of iodine per day may be at least as effective as a standard dose of 150 micrograms of thyroxine to treat endemic goitre in an iodine deficient area.     

Correlation between thyroid-follicle fusion and structural modifications of the epithelial cells

Summary Changes in thyroid structure induced by a decrease in TSH or iodide-dependent stimulation were quantified by stereological analysis of light micrographs. Studies were carried out on intact (R5) and hypophysectomized (R 5H) rats receiving 5 g iodide, and on intact rats (R5O) receiving 50 g iodide daily.For R 5H- and R5O-thyroids, the mean parameters of the epithelial cells, height, volume and lateral membrane area, were smaller than those of R 5-thyroids. An inverse shift was observed for the apical membrane area, whereas the peripheral membrane area was unchanged. The number of epithelial cells was similar in each of the three groups; however, the number of follicles was greater in R 5-thyroids, suggesting that follicular fusion occurs in R 5O- and R 5H-thyroids. This was confirmed by direct observation.The present results demonstrate that in adult rats a lack of TSH or an increased iodide diet (insufficient to produce a physiopathological state) induce follicle fusion probably by means of cellular reorganization. This increase in follicle size could be involved in the regulation of thyroid iodine turnover.     

Effect of vitamin E on follicular cell proliferation and expression of apoptosis-associated factors in rats with 6-N-propyl-2-thiouracil-induced goitrogenesis

We have investigated immunohistochemically the effect of dl-alpha-tocopherol (vitamin E) on thyroid gland with 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats. The animals were divided into four groups. Rats in group I were designated as control, rats in group II were treated with injections of PTU (10 mg/kg) for 15 days, rats in group III were treated with injections of PTU+vitamin E (10 mg/100 g) for 15 days. Rats in group IV were treated with injections PTU for 15 days and kept for 15 next days after cessation of PTU treatment. At the end of experiment, the animals were killed by decapitation, blood samples were obtained, thyroid tissues were collected and processed for quantitative evaluation of immunohistochemical PCNA (marker of cell proliferation), Bax (pro-apoptotic marker) and Bcl-2 (anti-apoptotic marker) staining. There was an increase in the number of PCNA-immunopositive cells in follicular epithelial cells of group II rats compared with other groups (p<0.05). After vitamin E treatment, the number of PCNA-immunopositive cells decreased (p<0.05) while the number of Bax-immunopositive cells increased (p<0.05). The number of Bcl-2-positive follicular epithelial cells of group IV rats was higher than in those of other groups (p<0.05). The results of this study indicate that hypothyroidism induces cell proliferation in the thyroid gland and vitamin E may promote involution of the gland.     

Role of iodine in antioxidant defence in thyroid and breast disease

The role played in thyroid hormonogenesis by iodide oxidation to iodine (organification) is well established. Iodine deficiency may produce conditions of oxidative stress with high TSH producing a level of H_2O_2, which because of lack of iodide is not being used to form thyroid hormones. The cytotoxic actions of excess iodide in thyroid cells may depend on the formation of free radicals and can be attributed to both necrotic and apoptotic mechanisms with necrosis predominating in goiter development and apoptosis during iodide induced involution. These cytotoxic effects appear to depend on the status of antioxidative enzymes and may only be evident in conditions of selenium deficiency where the activity of selenium containing antioxidative enzymes is impaired. Less compelling evidence exists of a role for iodide as an antioxidant in the breast. However the Japanese experience may indicate a protective effect against breast cancer for an iodine rich seaweed containing diet. Similarly thyroid autoimmunity may also be associated with improved prognosis. Whether this phenomenon is breast specific and its possible relationship to iodine or selenium status awaits resolution.     

Clinical study on early changes in thyroid function of hyperthyroidism treated with propylthiouracil and a relatively small dose of iodide.

In order to compare the acute effects of three kinds of antithyroid agents of iodide (I-), propylthiouracil (PTU) and PTU combined with iodide (PTU+I-) on thyroid function in hyperthyroid patients with diffuse goiter, serum concentrations of thyroxine (T4), triiodothyronine (T3), T3-resin sponge uptake (T3-RU) and free thyroxine index (FT4I) were employed as thyroid function parameters. In the group given iodine (1 mg/day) as iodinated-lecithine, the initial values of T4, T3, T3-RU and FT4I were 20.9 +/- 1.6 microng/100 ml (T4), greater than 740 ng/100 ml (T3), 49.5 +/- 2.3% (T3-RU) and 14.7 +/- 1.8 (FT4I). At the end of one week of therapy, they decreased clearly to 15.6 +/- 2.2 microng/100 ml, 457 +/- 87 ng/100 ml, 42.2 +/- 4.0% and 9.7 +/- 2.4. The so-called "escape phenomenon" from iodide inhibition was observed in serum T4, T3-RU and FT4I values at the end of two weeks of iodide therapy, while serum T3 continued to decrease but the value of T3 was far outside of the normal range. In the PTU group (300 mg/day), thyroid function parameters were 22.5 +/- 0.8 microng/100 ml (T4), greater than 592 ng/100 ml (T3), 54.9 +/- 1.0% (T3-RU) and 18.7 +/- 1.0 (FT4I) before treatment. They decreased continually week by week. At the end of four-week treatment with PTU, the value of each thyroid function parameter was 11.1 +/- 1.9 microng/100 ml, 229 +/- 56 ng/100 ml, 36.6 +/- 4.4% and 5.7 +/- 1.7. In the group of hyperthyroidism simultaneously given both PTU and iodide (300 mg/PTU and 1 mg/iodine), these thyroid function parameters decreased as well as in the group treated with PTU alone for more than two weeks. More rapid or significant decrease of T4, T3, T3-RU and ft4i in PTU+I- group than in PTU group was observed in the present study. These results suggested strongly that iodide alone was not an adequate therapy for hyperthyroidism as well known and they were also compatible with the idea that the concomitant administration of PTU and iodide was more effective in the early phase of therapy of hyperthyroidism than PTU alone.     

Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups

In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams.     

Thyroid function and polyamines. III. Changes in ornithine decarboxylase activity and polyamine contents in the rat thyroid during hyperplasia and involution

Changes in ornithine decarboxylase (ODC) activity and in polyamine contents of the rat thyroid were studied under various experimental conditions. Methylthiouracil (MTU) treatment produced several-fold increases in the thyroid ODC activity and in the content of putrescine, spermidine and spermine within a week. While serum thyrotropin (TSH) levels increased gradually up to 3 weeks, the content of both putrescine and spermidine tended to reach a plateau after 2 weeks of the goitrogen treatment; spermine content continued to increase progressively for 3 weeks. Discontinuance of MTU at 7 days resulted in a rapid decline in the elevated thyroid ODC activity, followed by a diminution of putrescine, spermidine and RNA contents. Thyroidal putrescine, spermidine and RNA responded more sensitively to both introduction and withdrawal of TSH stimulation than thyroidal spermine and DNA. Excess iodide, having no effect on the basal level of thyroid ODC, suppressed the MTU-induced increase in this enzyme activity without affecting circulating TSH, thyroxine (T4) and triiodothyronine (T3) levels. There was a significant negative correlation between the ODC activity and intrathyroidal concentration of iodine in MTU-pretreated rats. Theophylline increased the thyroid weight and ODC activity when given to rats fed with a subeffective dose of MTU. Analyses of serum TSH, T4, T3 and of thyroidal iodine revealed that TSH-induced thyroid ODC activity was suppressed by increased circulating thyroid hormones and/or intrathyroidal iodine. Furthermore, it was suggested that thyroid hormones and excess iodide acted directly on the thyroid to alter polyamine biosynthesis, possibly by changing the responsiveness of the gland to TSH.     

Regulation of thyroid cell volumes and fluid transport: opposite effects of TSH and iodide on cultured cells

Cell volume regulation by thyrotropin (TSH) and iodide, the main effectors involved in thyroid function, was studied in cultured thyroid cells. The mean cell volume, determined by performing 3-D reconstitution on confocal microscopy optical slices from living octadecylrhodamine-labeled cells cultured with both TSH and iodide (control cells), was 3.73 +/- 0.06 pl. The absence of iodide resulted in cell hypertrophy (136% of control value) and the absence of TSH in cell shrinkage (81%). These changes mainly affected the cell heights. The effect of TSH on cell volume was mediated by cAMP. The proportion of cytosolic volume (3-O-methyl-D-glucose space vs. total volume) decreased in the absence of iodide (85% of control value) and increased in the absence of TSH (139%), whereas protein content showed the opposite changes (121 and 58%, respectively). The net apical-to-basal fluid transport was also inversely controlled by the two effectors. Iodide thus antagonizes TSH effects on cell volumes and fluid transport, probably via adenylylcyclase downregulation mechanisms. The absence of either iodide or TSH may mimic the imbalance occurring in pathological thyroids.     

The goitrogen 3-hydroxy-4(1H)-pyridone, a ruminal 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.     

Clinical importance of reversibility in primary goitrous hypothyroidism.

Twenty seven hypothyroid patients with a serum concentration of thyroid stimulating hormone (TSH) of over 40 mU/1 were followed up for three to 20 weeks without replacement therapy. The serum thyroid hormone concentrations increased with a dramatic decrease in serum TSH values in 14 patients (reversible group) but there was no significant change in the other 13 (irreversible group). Fourteen out of 19 patients with goitre but none of the eight patients without goitre belonged to the reversible group. All of the 11 patients with a high uptake of iodide by the thyroid, three of the six with a normal uptake, and none of the 10 with a low uptake belonged to the reversible group. These observations indicate that patients with goitrous hypothyroidism with a preserved thyroid uptake of iodide are likely to become euthyroid spontaneously without replacement therapy.     

Nonresponsiveness of the thyroid gland to goitrogen in the early neonatal period in the rat: light- and electron-microscopic observations.

The thyroid response of fetal and neonatal rats to propylthiouracil (PTU) as a goitrogen was studied with observation of the thyroid glands by light and electron microscopy. On day 19 of gestation and on days 1, 3, 5 and 8 after birth, fetal and neonatal rats were given a subcutaneous injection of PTU and were autopsied 2 days later. PTU induced conspicuous goiters in fetal rats but did not in neonatal rats aged up to day 5 after birth. Beyond that age, PTU again induced goiters. Histologically, the follicular cell height in goitrous thyroid glands was significantly increased. Ultrastructurally, follicular cells in goitrous thyroid glands often had colloid droplets and lysosomes. It seems that nonresponsiveness of the thyroid glands in early neonatal rats to goitrogen is due to a temporary decline of the pituitary activity of thyrotropin secretion. About 5 days or more after birth, the pituitary-thyroid system begins to operate again in response to goitrogen.     

Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation of regulation and long-term programming of responses.

To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.     

Iodine-Induced Thyroid Blockade: Role of Selenium and Iodine in the Thyroid and Pituitary Glands

The purpose of this study was to determine the content of iodine and selenium in the thyroid and pituitary glands of rats under iodine-induced blockade of the thyroid gland. Electron probe microanalysis, wavelength-dispersive spectrometry, and point analysis were used in this investigation. We also determined the expression of sodium iodide symporter and caspase 32 in the thyroid and pituitary glands and the expression of thyroid-stimulating hormone in the pituitary. The samples for iodine analysis must be thoroughly dehydrated, and for this purpose, we developed a method that produced samples of constant mass with minimal loss of substrate (human thyroid gland was used for the investigation). Normal levels of iodine and selenium were found in the thyroid, pituitary, ovaries, testes hypothalamus, and pancreas of healthy rats. The levels of iodine and selenium in I- or Se-positive points and the percentage of positive points in most of these organs were similar to those of controls (basal level), except for the level of iodine in the thyroid gland and testes. Blockade of the thyroid gland changed the iodine level in iodine-positive points of the thyroid and the pituitary glands. On the sixth day of blockage, the iodine level in iodine-positive points of the thyroid gradually decreased to the basal level followed by an abrupt increase on the seventh day, implying a rebound effect. The opposite was found in the pituitary, in which the level of iodine in iodine-positive points increased during the first 6 days and then abruptly decreased on the seventh day. Expression of the thyroid-stimulating hormone in the pituitary decreased during the first 5 days but sharply increased on the sixth day, with a minimum level of iodine in the thyroid and maximum in the pituitary, before normalization of the iodine level in both glands preceding the rebound effect. The expression of sodium iodide symporter increased during the first 4 days of blockage and then decreased in both glands. The fluctuations of the thyroid-stimulating hormone in the pituitary gland reflected the changes of iodine in the thyroid gland more precisely than the changes of sodium iodide symporter. The selenium level in the selenium-positive points changed only in the pituitary, dropping to zero on the second and fifth day of the blockade. Simultaneously, the maximum induction of caspase 32 was observed in the pituitary gland. We believe that these results may help to clarify a role of the pituitary gland in the thyroid blockade.