Different tissue responses for iodine and iodide in rat thyroid and mammary glands

This research describes the effects of short-term elemental iodine (I₂) and iodide (I⁻) replacement on thyroid glands and mammary glands of iodine-deficient (ID) Sprague-Dawley female rats. Iodine deficiency causes atypical tissue and physiologic changes in both glands. Tissue histopathology and the endocrine metabolic parameters, such as serum TT₄, tissue and body weights, and vaginal smears, are compared. A moderate reduction in thyroid size from the ID control (IDC) was noted with both I⁻ and I₂, whereas serum total thyroxine approached the normal control with both I⁻ and I₂, but was lower in IDC. Thyroid gland IDC hyperplasia was reduced modestly with I₂, but eliminated with I⁻. Lobular hyperplasia of the mammary glands decreased with I₂ and increased with I⁻ when compared with the IDC; extraductal secretions remained the same as IDC with I₂, but increased with I⁻; and periductal fibrosis was markedly reduced with I₂, but remained severe with I⁻. Thus, orally administered I₂ or I⁻ in trace doses with similar iodine availability caused different histopathological and endocrine patterns in thyroid and mammary glands of ID rats. The significance of this is that replacement therapy with various forms of iodine are tissue-specific.     

Histological and ultrastructural alterations of rat thyroid gland after short-term treatment with high doses of thyroid hormones

The aim of the present study was to investigate histological alterations of rat thyroid gland after short-term treatment with supraphysiological doses of thyroid hormones. Rats from experimental groups were treated with triiodothyronine (T3) or thyroxine (T4) during five days. In both treated groups, thyrocyte height was reduced and follicular lumens were distended. Progressive involutive changes of the thyroid parenchyma were apparent, including follicular remodeling (fusion) and death of thyrocytes. Morphological changes confirmed by quantitative analysis were more pronounced in the T4-treated group. Our results demonstrate that thyrotoxicosis, whether induced by T3 or T4, leads to different grades of thyroid tissue injury, including some irreversible damages. These changes might be explained at least in part by lack of trophic and cytoprotective effects of the thyroid stimulating hormone. Since the period required for morphophysiological recovery may be unpredictable, findings presented here should be taken into consideration in cases where the thyroid hormones are used as a treatment for thyroid and non-thyroid related conditions.     

Acute effects of various doses of iodide on thyroid iodine autoregulation

Analytical ion microscopy (AIM) was used to determine alterations in the thyroid follicular lumen¹²⁷I stores of Wistar rats injected with different doses of¹²⁹I (low specific activity radionuclide). Animals fed a normal iodine diet (10 μg¹²⁷I/d) were divided into four groups: control group and three treated groups injected ip 24 h before sacrifice with¹²⁹I at doses of 10 μg (group 1), 30 μg (group 2), and 8500 μg (group 3). AIM was performed on thyroid semithin sections. The mean¹²⁹I concentration increased with the dose injected from group 1 (0.44±0.03 μg/mg, mean ± SEM) to group 2 (2.05±0.14 μg/mg) and decreased in group 3 (0.57±0.08 μg/mg). When compared to control group (4.14±0.17 μg/mg), the mean¹²⁷I concentration was not changed in group 1 (4.52±0.07 μg/mg), but altered in the other groups: It was significantly increased (7.14±0.41 μg/mg) in group 2 and slightly decreased (3.11±0.26 μg/mg) in group 3. These results underline the interest of AIM in the study of the effects of various doses of iodide on the thyroid autoregulation by iodide, a trace element actively trapped by this gland.     

Cytochemical localization of hydrogen peroxide generating sites in the rat thyroid gland

Sites of H₂O₂ generation in lightly prefixed, intact thyroid follicles were studied by two cytochemical reactions: peroxidase-dependent DAB oxidation and cerium precipitation. In both cases reaction product accumulated on the apical surface of the follicle cell at the membrane-colloid interface. The former reaction was inhibited by the peroxidase inhibitor, aminotriazole; both reactions were blocked by the presence of catalase. NADH in the medium slightly increased the amount of cerium precipitation. The ferricyanide technique for oxidoreductase activity was also applied; reaction product again was associated with the apical surface. These results strongly imply that the follicle cells have a NADH oxidizing system generating H₂O₂ at the apical plasma membrane.     

Determination of iodide using flow injection with acidic potassium permanganate chemiluminescence detection.

A simple and rapid flow-injection method is described for the determination of iodide, based on potassium permanganate chemiluminescence detection via oxidation of formaldehyde in aqueous hydrochloric acid. The calibration graph was linear over the range 1.0-12 x 10(-6) mol/L (r2 = 0.9955) with relative standard deviations (n = 4) in the range 1.0-3.5%. The detection limit (3sigma) was 1.0 x 10(-7) mol/L, with sample throughput of 120/h. The effect of interfering cations [Ca(II), Mg(II), Ni(II), Fe(II), Fe(III) and Pb(II)] and anions (Cl-, SO4(2-), PO4(3-), NO3-, NO2-, F- and SO3(2-)) were studied. The method was applied to iodized salt samples and the results obtained in the range 0.03 +/- 0.005 - 0.10 +/- 0.006 mg I/g were in reasonable agreement with the amount labelled. The method was statistically compared with the results obtained by titration; no significant disagreement at 95% confidence was observed.     

The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism

Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases, which convert thyroxine (T₄) to the more metabolically active 3,3′-5 triiodothyronine (T₃). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [¹²⁵I]N-bromoacetyl reverse triiodothyronine, is also labeled with⁷⁵Se by in vivo treatment of rats with⁷⁵Se-Na₂SeO₃. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent selenium deficiency could be a major determinant of the severity of iodine deficiency.     

The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism

Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases, which convert thyroxine (T₄) to the more metabolically active 3,3′–5 triiodothyronine (T₃). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [¹²⁵I]N-bromoacetyl reverse triiodothyronine, is also labeled with⁷⁵Se by in vivo treatment of rats with⁷⁵Se−Na₂SeO₃. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent selenium deficiency could be a major determinant of the severity of iodine deficiency.     

Propranolol has direct antithyroid activity: Inhibition of iodide transport in cultured thyroid follicles

The effect of propranolol on the process of thyroid hormone formation was studied in a physiological culture system. Porcine thyroid follicles were preincubated with propranolol for 24 h. Iodide transport, iodine organification, and de novo thyroid hormone formation were measured by incubating these follicles with the mixture of carrier-free 0·1 μCi Na ¹²⁵I and 50 nM NaI for 2 to 6 h at 37°C. A concentration of propranolol greater than 100 μM inhibited iodide transport in a dose-dependent manner; this inhibition was non-competitive with iodide and independent of thyrotropin (TSH). Reduced iodine organification and thyroid hormone formation was seen with 150 μM propranolol or greater. The inhibitory action of propranolol was not caused by beta-blocking activity, since D -propranolol (devoid of beta-blocking activity) inhibited iodide transport, and other beta-blockers (metoprolol, atenolol, and labetalol) did not inhibit iodide transport. The inhibition of iodide transport was most likely caused by membrane stabilizing activity since quinidine, which possess the same membrane stabilizing activity as propranolol, also inhibited iodide transport. TSH-mediated cAMP generation and Na ⁺K⁺ ATPase activity, membrane functions for iodide transport, were unaffected by propranolol. Our study has shown, for the first time, that propranolol has a direct antithyroid action, namely inhibition of iodide transport in the intact thyroid follicle.     

Interaction of bromine with iodine in the rat thyroid gland at enhanced bromide intake

In experiments with rats, we have found that at enhanced intake of bromide, bromine does not replace chlorine in the thyroid; it replaces iodine. Under our experimental conditions, more than onethird of the iodine content in the thyroid was replaced by bromine. In the thyroid, bromine probably remained in the form of bromide and, in proportional to its increased concentration, the production of iodinated thyronines decreased, with the sum of the iodine and bromine concentrations being constant at the value of 20.51±1.16 μmol/g dry wt of the thyroid. In contrast to other organs, the biological behavior of bromine in the thyroid is not similar to the biological behavior of chlorine but resembles more that of iodine.     

Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats

Sex steroids interfere with the pituitary-thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demonstrate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a significant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal.     

Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure

The effects of supplementing selenium on thyroid hormone metabolism were studied on mice with excessive iodine exposure. The serum concentrations of thyroxine (T₄) and triiodothyronine (T₃) and the activities of iodothyronine 5′ and 5-deiodinase (D2, D3) were measured in the brain of filial mice to study the influence of selenium on thyroid hormone metabolism. Measurements were carried out on postnatal day 0, 14, and 28. It was found that selenium supplementation alleviated the adverse effects of excessive iodine on progeny. The serum TT₄ level as well as TT₄ and TT₃ concentrations and D3 activity in cerebrum of progeny decreased, whereas D2 activity increased in the cerebrum of progeny on postnatal day 0 and 14. Selenium supplementation exerted some favorable effects on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine intake.     

The effect of mildronate and related substances on levels of thyroid hormones and some intermediates of lipid and carbohydrate metabolism in hyperthyroid and hypothyroid rats

The effects of mildronate [3(2,2,2-trimethylhydrazinium) propionate dihydrate], γ-butyrobetaine (GBB) and their combination (neomildronate) on the level of thyroid hormones and some intermediates of basal metabolism (free fatty acids, triglycerides, glucose) in serum of laboratory rats with various dysfunctions of thyroid glands including idiopathic hyperfunction and also hypofunction induced by administration of 6-propyl-2-thiouracil (PTU) or L-carnitine administration. Intraperitoneal injections of mildronate (150 mg/kg) during 20 days to male Wistar rats with elevated level of thyroid hormones and basal metabolism normalized thyroxin level and parameters of lipid metabolism in serum. Administration of the compounds studied to rats with hypothyroidism induced by administration of PTU or L-carnitine did not influence natural recovery of the hormonal level. Possible biochemical role of these pharmacological treatments is discussed in terms of in regulation of thyroid gland function.     

Effect of selenium supplementation on thyroid hormone levels and selenoenzyme activities in growing lambs

The aim of the present study was to evaluate the effects of selenium supplementation on thyroid hormone metabolism and selenoenzyme activities in lambs. Twelve 20-d-old male lambs were assigned to one of two diets: A (0.11 ppm Se) and B (supplemented with 0.2 ppm selenium as sodium selenite). Blood samples were collected weekly for the determination of T₃, T₄, and selenium levels. The response to thyrotropin-releasing hormone (TRH) challenge was estimated at the 11th and 20th wk. Animals were slaughtered at wk 20 and tissues were collected for enzyme determination. Plasma selenium concentration was significantly higher in supplemented lambs (p<0.001). Plasma T₃ and T₄ levels remained similar in both groups. Type I deiodinase activity (ID-I) was decreased in the liver (p<0.05) and increased in the pituitary (p<0.01) of supplemented animals. No ID-I activity was detected in the thyroid. Pituitary type II deiodinase activity (ID-II) remained unchanged. The response to TRH challenge did not differ between the two groups for both challenges, but in group B, the second TRH challenge (20th wk) resulted in a significantly higher T₃ response compared to the first one (11th wk) (p<0.05). In conclusion, the lack of effects of Se supplementation on thyroid hormone metabolism demonstrates that enzyme activity is homeostatically controlled and selenium is incorporated in that order to ensure the maintenance of thyroid hormone homeostasis.     

High bromide intake affects the accumulation of iodide in the rat thyroid and skin

The effect of a high bromide intake on the kinetics of iodide uptake and elimination in the thyroid and skin of adult male rats was studied. In rats fed a diet with sufficient iodine supply (>25 μg I/d), the iodide accumulation in the skin predominated during the first hours after ¹³¹I -iodide application. From this organ, radioiodide was gradually transferred into the thyroid. A high bromide intake (>150 mg Br⁻/d) in these animals led to a marked decrease in iodide accumulation, especially by the thyroid, because of an increase in iodide elimination both from the thyroid and from the skin. In rats kept under the conditions of iodine deficiency (<1 μ I/d), the iodide accumulation in the thyroid, but not in the skin, was markedly increased as a result of a thyrotropic stimulation. The effect of a high bromide intake (>100 mg Br⁻/d) in these animals was particularly pronounced because the rates of iodide elimination were most accelerated both from their thyroid and from their skin. Presented in part at the 20th Workshop on Macro and Trace Elements held in Jena (Germany) on December 1–2, 2000.     

The effect of long-term external ionizing radiation on the functional activity of rat thyroid under enhanced potassium iodide consumption

The study was devoted to the effect of long-term (20 days) external ionizing radiation at a dose of 0.5 Gy on the iodide metabolism in the rat thyroid under supplementation of high iodine doses (10 daily KI doses). It was found that the potassium iodide administration partially prevented the effects of a post radiation decrease of serum thyroid hormone levels (the level of T4 was normal and that of T3 was 77.4% of the controls). After the supplementation of 10 daily iodide doses, the rat thyroid tissue showed the most pronounced increase in the levels of total, free and protein-bound iodide compared to the groups of animals consuming normal and elevated KI doses. Pronounced inhibition of thyroid peroxidase activity (3.1-fold) was noted in the same group. The data obtained indicate a radiation-induced activation of iodide uptake during its enhanced supplementation and disturbed iodide enzymatic oxidation and organification.     

Effect of prolactin on maintenance of prelactating human mammary gland in vitro

Summary Human mammary tissue from a female at the end of the second trimester of pregnancy was studied in organ culture in a chemically defined medium. Sampling was carried out at 1, 2 and 3 weeks. Without hormones, there was nearly total lobuloalveolar degeneration inall specimens at all times. Addition of insulin, hydrocortisone and ovine prolactin, in combination at a concentration of 5 μg per ml each, did not affect the extent of degeneration. Raising the concentration of prolactin to 50 μg per ml resulted in greatly improved lobulo-alveolar maintenance inall specimens and continued epithelial cell DNA synthesis for up to 3 weeks in vitro. This work was supported by grant no. CA11536 from the National Cancer Institute.     

Further studies on the regulation of the Harderian glands of golden hamsters by the thyroid gland

Summary Long-term increased or decreased circulating levels of thyroid hormones significantly modify porphyrin concentrations and morphology in the Harderian glands of male and female hamsters. Administration of T₃ reduced porphyrin concentrations in females; this treatment or decreasing thyroid hormone levels with KClO₄ suppressed the post-castration rise of porphyrins in males. Hypophysectomy led to increased porphyrins in the Harderian glands of males; this rise was suppressed in hypophysectomized males by T₃ or T₄. In females, hypophysectomy reduced porphyrins which were further reduced by daily administration of T₃ or T₄. These modifications in the normal females were identical in castrated males. Mitotic activity in the Harderian glands of females was stimulated by KClO₄ and by hypophysectomy with or without exogenous T₃. In males, castration increased mitotic activity which was suppressed by T₃ and exacerbated by KClO₄. Increased mitotic activity seemingly follows loss of tissue mass. The data show that thyroid hormones act directly on the Harderian glands rather than indirectly through modification of TSH synthesis/release. Female type glands in males are a consequence of loss of gonadal androgens by castration, or by suppression or loss of thyroid hormones by hypophysectomy or by treatment with KClO₄. However, male type glands in females are the result of androgen treatment, and/or increased levels of thyroid hormones via reduced ambient temperatures or of photic input. We conclude that regulation of the Harderian gland appears to be different in the two sexes.Abbreviations T ₃ Triiodothyronine - T ₄ Thyroxine - TSH Thyroid Stimulating Hormone - KClO ₄ Potassium Perchlorate - h hours - ml milliliter - mg milligram - g gram - male - female - castrated male - AP hypophysectomized - CON Control - ALA delta aminole-vulenic acid - HG Harderian Gland     

Effect of repetitive potassium iodide on thyroid and cardiovascular functions in elderly rats

BackgroundTo date, paediatric thyroid cancer has been the most severe health consequence of the Chernobyl accident, caused by radioactive iodine (¹³¹I) aerosol's dispersion. WHO recommends a single dose of potassium iodide (KI) to reduce this risk. Following the Fukushima accident, it became obvious that repetitive doses of KI may be necessary due to multiple exposures to ¹³¹I. Knowledge about the effects of repeated ITB (Iodine Thyroid Blocking) is scarce and controversial. KI may affect the thyroid hormones synthesis; which is crucial for the cardiovascular function. Furthermore, myocardial and vascular endothelial tissues are sensitizes to subtle changes at the concentration of circulating pituitary and/or thyroid hormones.ObjectiveIn this preclinical study, we aimed to assess the effects of repeated ITB in elderly male rats.MethodsTwelve months old male Wistar rats were subjected to either KI or saline solution for eight days. Analyses were performed 24 h and 30 days after the treatment discontinuation.FindingsWe reported a significant increase (18%) in some urinary parameters related to renal function, a subtle decrease of plasma TSH level, a significant increase (379%) in renin and a significant decrease (50%) in aldosterone upon KI administration. At the molecular level, the expression of thyroid and cardiovascular genes was significantly affected by the treatment. However, in our experimental settlement, animal heart rate was not significantly affected thirty days after KI discontinuation. ECG patterns did not change after administration of KI, and arrhythmia was not observed in these conditions despite the PR-intervals decreased significantly. Cardiovascular physiology was preserved.ConclusionOur results indicate that repeated ITB in elderly rats is characterized by molecular modifications of cardiovascular key actors, particularly the Renin-angiotensin-aldosterone axis with a preserved physiological homeostasis. This new scientific evidence may be useful for the maturation of ITB guidelines especially for elderly sub-population.     

Effects of potassium iodide on the growth and metabolite accumulation of two planktonic diatoms

In this study the effects of potassium iodide on the growth and metabolite accumulation of Nitzschia closterium (Ehr.) W. Smith and Phaedactylum tricornutum Bolin were investigated to assess its possible application to the mass culture of the two diatoms in open environment, extensive systems. The results indicated that supplementation of potassium iodide at a concentration of 1000 mg L⁻¹ resulted in a reduction of the induction phase in cultures of N. closterium and P. tricornutum and led to an increase in the accumulation of biomass and extracellular polymeric substances. Conversely, the addition of potassium iodide, at all concentrations tested, showed no obvious effect on the fatty acid profiles of the two diatoms, particularly in the content of eicosapentaenoic and decosahexaenoic acid. Potassium iodide was also found to inhibit the growth of Dunaliella salina, Cryptomonas sp. and Chlorella sp. at minimum inhibitory concentrations of 356.8, 475.9 and 696.2 mg L⁻¹, respectively. It also inhibited bacteria, including species isolated from the two diatom cultures, at a minimum concentration of 400 mg L⁻¹. These results suggest that potassium iodide is an effective agent for inhibiting the proliferation of certain flagellate and non-flagellate algae, and bacteria, thus forming a favorable environment for diatoms to proliferate and consequently improving accumulation of biomass and EPS. These properties of potassium iodide provide a possible solution for preventing contamination from flagellate and non-flagellate algae in mass culture of the two diatoms without causing significant changes in their fatty acid composition.