Sample records for goitrogens
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Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.) 1
Elliott, Malcolm C.; Stowe, Bruce B.
1971-01-01
Five conspicuous indole derivatives are present in leaves and other tissues of woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B, glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter three indole glucosinolates are present at levels of at least 260, 69, and 200 milligrams per kilogram fresh weight and were isolated as crystalline salts. Comparison of physical and chemical properties, particularly NMR spectral analysis, confirms that the 1-methoxyglucobrassicin structure suggested for neoglucobrassicin is correct, whereas further evidence for the even more unusual sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained. Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that of glucobrassicin. As it too releases thiocyanate, it must be added to the list of known plant goitrogens. These studies and the techniques described establish woad as exceptionally suitable higher plant material for metabolic studies of indoles related to goitrogens and auxins. PMID:16657624
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Indole Compounds Related to Auxins and Goitrogens of Woad (Isatis tinctoria L.).
Elliott, M C; Stowe, B B
1971-03-01
Five conspicuous indole derivatives are present in leaves and other tissues of woad (Isatis tinctoria L.). They were identified as tryptophan, isatan B, glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate. The latter three indole glucosinolates are present at levels of at least 260, 69, and 200 milligrams per kilogram fresh weight and were isolated as crystalline salts. Comparison of physical and chemical properties, particularly NMR spectral analysis, confirms that the 1-methoxyglucobrassicin structure suggested for neoglucobrassicin is correct, whereas further evidence for the even more unusual sulfonation of the ring nitrogen in glucobrassicin-1-sulfonate was obtained. Glucobrassicin-1-sulfonate has an enzymic degradation pattern identical to that of glucobrassicin. As it too releases thiocyanate, it must be added to the list of known plant goitrogens. These studies and the techniques described establish woad as exceptionally suitable higher plant material for metabolic studies of indoles related to goitrogens and auxins.
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Kurnaz, Erdal; Savaş-Erdeve, Şenay; Keskin, Melikşah; Doğan, Vehbi; Çetinkaya, Semra; Aycan, Zehra
2016-01-01
The most common reason of acquired hypothyroidism is autoimmune (Hashimoto) thyroiditis. Autoimmune thyroiditis can be atrophic or goitrogenic. Atrophic autoimmune thyroiditis (ATT) related acquired hypothyroidism causes interruption of growth, obesity, and bone age retardation in early ages while goitrogenic thyroiditis has a higher incidence rate and mostly presents with diffuse goiter. We discuss the effects of hypothyroidism on various systems through a case found to have pericardial effusion during the echocardiography performed after cardiac murmur was detected and later diagnosed with ATT related hypothyroidism.
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Dietary patterns, goitrogenic food, and thyroid cancer: a case-control study in French Polynesia.
Cléro, Énora; Doyon, Françoise; Chungue, Vaïana; Rachédi, Frédérique; Boissin, Jean-Louis; Sebbag, Joseph; Shan, Larrys; Rubino, Carole; de Vathaire, Florent
2012-01-01
French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 229 cases of differentiated thyroid cancer diagnosed between 1979 and 2004, and 371 population controls. Dietary patterns and goitrogenic food consumption (cabbage, cassava) were analyzed. We used a factor analysis to identify dietary patterns and a conditional logistic regression analysis to investigate the association between dietary patterns or food items and thyroid cancer risk. Two distinct dietary patterns were identified: traditional Polynesian and Western. A nonsignificant inverse association was observed between the traditional Polynesian dietary pattern and thyroid cancer risk. The Western pattern was not associated with thyroid cancer risk. Cassava consumption was significantly associated with a decreased risk of thyroid cancer. In conclusion, a traditional Polynesian dietary pattern led to a weak reduced risk of thyroid cancer in French Polynesia. The protective effect of cassava on this cancer does not seem to be substantially different from that of cabbage, which was the main goitrogenic food studied to date.
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Sharma, Prakash; Patino, Reynaldo
2013-01-01
We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent.
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Sharma, Prakash; Patiño, Reynaldo
2013-04-01
We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent. Published by Elsevier Inc.
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Bath, G F; Wentzel, D; van Tonder, E M
1979-12-01
An outbreak of goitre and hypothyroidism in newborn Angora kids is described. the does had been grazing on lucerne from the time of mating and received a free-choice lick, which included iodine. Investigations revealed that the condition was iodine-responsive, and was probably caused by a goitrogen like thiocyanate.
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Many developmental events are regulated at least in part by thyroid hormones. It was hypothesized that tissue biomarkers of thyroid status would be more accurate predictors of neurotoxicity than serum biomarkers in rats treated with the goitrogen propylthiouracil (PTU). Over seve...
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NEURONS COMPRISING A HETEROTOPIA INDUCED BY DEVELOPMENTAL HYPOTHYROIDISM ARE BORN LATE IN GESTATION.
We previously described an abnormal cluster of neurons, a heterotopia, located in the corpus callosum in rat pups born to dams exposed to the goitrogen, propylthiouracil (PTU, Goodman et al., SfN 2004). In this study we determined 1) whether the formation of the heterotopia was u...
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Lactational exposure to 6-propyl-2-thio-uracil (PTU), a neonatal goitrogen, leads to increased testis size and sperm production in rodents. Aktl, a gene involved in cell survival and proliferation is also phosphorylated by thyroxine (T4). Therefore, we examined the requirement f...
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Humans and wildlife are exposed to environmental pollutants that have been shown to interfere with the thyroid hormone system and thus may affect brain development. Our goal was to expose pregnant rats to propylthiouracil (PTU) to measure the effects of a goitrogen on white matte...
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Platzer, S; Groebner, P; Hausen, A; Obendorf, L; Riccabona, G
1980-02-01
According to several reports we suspected that the pathogenesis of endemic goitre cannot be explained by iodine deficiency only, but that other--partially endogenous--goitrogenic factors must be present. We therefore studied 16 cases of "euthyroid" endemic goitre from the endemic goitre area of the province of Bolzano in Italy. After fractionation of tissue homogenates, T 4 and T 3 were measured by RIA and the I concentration was also termined. Thyroglobulin and its fractions were measured by ultracentrifuge procedures after assessment of the total protein concentration. Evaluation of the present results suggests that an insufficient synthesis of thyroglobulin in the examined goitres induces an inadequate adaptation of the organism to iodine deficiency, which, in turn, decreases the thyroid hormone concentration in thyroid tissue and enhances goitrogenesis. Considering the normal iodine content of the examined tissues, there obviously seems to be two intrathyroidal iodine pools, one of which supplies the body with thyroid hormones under pituitary stimulation even though its thyroglobulin pool is reduced, while a significant amount of the thyroidal iodine pool is bound in metabolically inert protein molecules and therefore increases the goitrogenic effect of iodine deficiency.
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Sharma, Prakash; Tang, Song; Mayer, Gregory D; Patiño, Reynaldo
2016-09-01
Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2nM), goitrogen [methimazole (MZ), 0.15mM], MZ (0.15mM) and T4 (2nM) (rescue treatment), or reconstituted water (control) from 3 to 33days postfertilization (dpf) and maintained in control water until 45dpf. Whole fish were collected during early (25dpf) and late (45dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45dpf and, unexpectedly, reduced expression of dmrt1 at 45dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its "feminizing" activity on gonadal sex is not permanent. Published by Elsevier Inc.
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Distribution and Variation of Indole Glucosinolates in Woad (Isatis tinctoria L.) 1
Elliott, Malcolm C.; Stowe, Bruce B.
1971-01-01
The exceptionally high levels in woad (Isatis tinctoria L.) of three indolic goitrogens, namely glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate, permit the facile study of their distribution in the plant and their changes during its development. Woad seeds contain as much as 0.23% fresh weight of glucobrassicin but no other indole glucosinolate, while 1-week-old seedlings also contain substantial amounts of neoglucobrassicin and glucobrassicin-1-sulfonate in their shoots whether grown in the light or dark. The sulfonate is not found in roots, and light depresses neoglucobrassicin levels in shoots. Sterile root cultures synthesize glucobrassicin and neoglucobrassicin, and significant quantities of these were even found to be excreted by the roots of intact sterile seedlings in culture. This may explain the long known deleterious effect of woad and other cruciferous crops on subsequent plantings and the observation could be of ecological importance. Long term changes in levels of all three substances in the plant are similar and are compatible with earlier suggestions that the compounds could be auxin precursors at the time of flower stem elongation. Since sterile seedlings readily incorporate 35SO42− into indole glucosinolates and relative specific radioactivities suggest that glucobrassicin is the precursor of the other two compounds, pathways of goitrogen biosynthesis should be relatively easily determined in this material. PMID:16657825
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Distribution and Variation of Indole Glucosinolates in Woad (Isatis tinctoria L.).
Elliott, M C; Stowe, B B
1971-10-01
The exceptionally high levels in woad (Isatis tinctoria L.) of three indolic goitrogens, namely glucobrassicin, neoglucobrassicin, and glucobrassicin-1-sulfonate, permit the facile study of their distribution in the plant and their changes during its development. Woad seeds contain as much as 0.23% fresh weight of glucobrassicin but no other indole glucosinolate, while 1-week-old seedlings also contain substantial amounts of neoglucobrassicin and glucobrassicin-1-sulfonate in their shoots whether grown in the light or dark. The sulfonate is not found in roots, and light depresses neoglucobrassicin levels in shoots. Sterile root cultures synthesize glucobrassicin and neoglucobrassicin, and significant quantities of these were even found to be excreted by the roots of intact sterile seedlings in culture. This may explain the long known deleterious effect of woad and other cruciferous crops on subsequent plantings and the observation could be of ecological importance. Long term changes in levels of all three substances in the plant are similar and are compatible with earlier suggestions that the compounds could be auxin precursors at the time of flower stem elongation. Since sterile seedlings readily incorporate (35)SO(4) (2-) into indole glucosinolates and relative specific radioactivities suggest that glucobrassicin is the precursor of the other two compounds, pathways of goitrogen biosynthesis should be relatively easily determined in this material.
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Hyperthyroidism in cats: what's causing this epidemic of thyroid disease and can we prevent it?
Peterson, Mark
2012-11-01
Since first being reported in the late 1970s, there has been a dramatic increase in the prevalence of hyperthyroidism in cats. It is now recognized worldwide as the most common feline endocrine disorder. Hyperthyroidism is an important cause of morbidity in cats older than 10 years of age. It is estimated that over 10% of all senior cats will develop the disorder. Despite its frequency, the underlying cause(s) of this common disease is/are not known, and no one has suggested a means to prevent the disorder. Because of the multiple risk factors that have been described for feline hyperthyroidism, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid disruptor chemicals or goitrogens in food or water, acting together in an additive or synergistic manner, may first lead to euthyroid goiter and then to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism. This review draws on published research studies to summarize the available evidence about the risk factors for feline hyperthyroidism. Based on the known goitrogens that may be present in the cat's food, drinking water or environment, it proposes measures that cat owners can implement that might prevent, or reduce the prevalence of, thyroid tumors and hyperthyroidism in their cats.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
E.Haut, J
Concern has been generated over the discovery of endocrine disrupting chemicals in rivers near sewage outflows. The presence of endocrine disrupting chemicals such as estradiol-17{beta} has been associated with a reduction of reproductive success in fish and an increase in the female phenotype and gonadal intersex in fish downstream of sewage treatment facilities. Such effects are believed to result from a disruption in the normal estrogenic pathways since estrogen plays a vital role in reproduction, sexual differentiation, the developments of secondary sex characteristics, and ovulation. Most studies have focused on the effect of a single endocrine disruptor on a singlemore » gene which does not provide for the interaction between genes. Microarray technology has made it possible to put an entire genome on a single chip so that researchers can get a clearer picture of the interaction of genes expressed in a cell and changes of said interactions when those cells are exposed to various conditions. Medaka males were exposed to known endocrine disruptors, estradial-17{beta} and goitrogen, and medaka females were exposed to flutamide. All treatments were then compared to controls. Total RNA was extracted from the livers of both treated and untreated males and hybridized to a microarray chip designed to have EST sequences specific to medaka. ESTs were identified through two-channel microarray analysis and compared to GenBank using blastn searches to identify up regulated genes. Choriogenins H and L, zona radiata, and vitellogenin, previously shown to be estrogen-induced in male fish were identified. Heat shock proteins (hsp70, hsp90, and hsp8) were also induced by estradiol-17{beta}, as was choriogenin Hminor. Exposure to goitrogen (T3) resulted in the induced expression of glutathione S-transferase and a GABA receptor protein in male medaka. Treatment with flutamide, an antiandrogen, caused the up regulation of choriogenin L, choriogenin Hminor, and zona radiata-2 in female medaka. Further study of the genes identified in this study may serve as possible biomarkers to signal the effects caused by the presence of endocrine disruptors and provide a screening mechanism for the presence of estrogens in the environment. Microarray technology may provide a means to screen multiple biomarkers simultaneously and provide a more rapid and accurate tool for assessing endocrine disruption due to environmental pollutants.« less
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Sharma, Prakash; Tang, Song; Mayer, Gregory D.; Patino, Reynaldo
2016-01-01
Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2 nM), goitrogen [methimazole (MZ), 0.15 mM], MZ (0.15 mM) and T4 (2 nM) (rescue treatment), or reconstituted water (control) from 3 to 33 days postfertilization (dpf) and maintained in control water until 45 dpf. Whole fish were collected during early (25 dpf) and late (45 dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45 dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45 dpf and, unexpectedly, reduced expression of dmrt1 at 45 dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45 dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25 dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its “feminizing” activity on gonadal sex is not permanent.
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Epidemiology of endemic goitre in western Colombia
Gaitan, E.; Merino, H.; Rodriguez, G.; Medina, P.; Meyer, J. D.; DeRouen, T. A.; MacLennan, R.
1978-01-01
This paper reports on recent epidemiological observations in western Colombia, which further demonstrate the presence of naturally-occurring goitrogens contaminating water supplies in areas where goitre persists despite prolonged and continuous iodine supplementation. 'Prospective' and 'cross-sectional' studies in 41 localities where the populations have been on a uniform and adequate iodine supplementation for the last 10-20 years indicate that, in the endemia of western Colombia, environmental factors other than nutritional iodine deficiency are responsible for differences in goitre prevalence. Further epidemiological studies to determine the causal factors for the persistence of the endemia established a correlation between the sources of drinking water and goitre prevalence rates. Organic compounds containing sulfur with marked thionamide-like antithyroid activity were isolated from water supplying endemic goitre districts, and results are presented supporting the hypothesis that sedimentary rocks rich in organic matter are the main source of water-borne goitrogens. Bacteriological investigations showed that the presence of Klebsiella pneumoniae in drinking water and bacterial concentration were related significantly with goitre prevalence only in the presence of other variables, particularly the presence of sedimentary rocks. In the light of these epidemiological observations and experimental studies it may be concluded that, at present, endemic goitre in western Colombia is not due to nutritional iodine deficiency, but that water supplies are contaminated with sulfur-bearing organic compounds with thionamide-like antithyroid activity most probably deriving from sedimentary rocks rich in organic matter and that these compounds are the main factor underlying the endemia. PMID:80287
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Metformin inhibits goitrogenous effects of type 2 diabetes.
Ittermann, Till; Markus, Marcello R P; Schipf, Sabine; Derwahl, Michael; Meisinger, Christa; Völzke, Henry
2013-07-01
Data on the association between type 2 diabetes mellitus (T2DM) and thyroid volume are sparse. An experimental study demonstrated an inhibitory effect of metformin on the growth of human thyroid cells. So far no study on humans has investigated potentially modulating effects of metformin on the association between T2DM and thyroid volume. Therefore, we investigated these effects in a population-based cohort study. We used data from the Study of Health in Pomerania and included 2570 individuals for cross-sectional and 1088 individuals for longitudinal analyses. T2DM was defined by physician-diagnosed self-report or intake of antidiabetic medication. In the cross-sectional data, females with T2DM treated with antidiabetic medication other than metformin had a larger thyroid volume (β=4.69; 95% CI 1.87 to 7.50) and a higher odds ratio (OR) for goiter (OR=1.71; 95% CI 1.05 to 2.79) than females without T2DM, whereas in males, no such association was detected. In females or males treated with metformin, T2DM was not associated with thyroid volume or goiter. In longitudinal analyses, incident T2DM not treated with metformin was significantly associated with a higher risk for incident goiter in the total population (incidence rate ratio (IRR)=1.70; 95% CI 1.10 to 2.91). Individuals with T2DM having changed from metformin to other antidiabetic agents during follow-up also had a higher risk for incident goiter than individuals without T2DM (IRR=2.71; 95% CI 1.74 to 4.20). We demonstrate an inhibitory effect of metformin on prevalent and incident goiter. Anti-goitrogenous effects of metformin add to the general benefits of metformin treatment of T2DM.
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Gangashetty, Prakash Irappa; Grando, Stefania; Kwaku Zu, Theophilus Tenutse; Daminati, Maria Gloria
2018-01-01
Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important “orphan” cereal and the most widely grown of all the millet species worldwide. It is also the sixth most important cereal in the world after wheat, rice, maize, barley, and sorghum, being largely grown and used in West Africa as well as in India and Pakistan. The present study was carried out in the frame of a program designed to increase benefits and reduce potential health problems deriving from the consumption of pearl millet. The specific goal was to provide a database of information on the variability existing in pearl millet germplasm as to the amounts of phytate, the most relevant antinutrient compound, and the goitrogenic compounds C-glycosylflavones (C-GFs) accumulated in the grain.Results we obtained clearly show that, as indicated by the range in values, a substantial variability subsists across the investigated pearl millet inbred lines as regards the grain level of phytic acid phosphate, while the amount of C-GFs shows a very high variation. Suitable potential parents to be used in breeding programs can be therefore chosen from the surveyed material in order to create new germplasm with increased nutritional quality and food safety. Moreover, we report novel molecular data showing which genes are more relevant for phytic acid biosynthesis in the seeds as well as a preliminary analysis of a pearl millet orthologous gene for C-GFs biosynthesis. These results open the way to dissect the genetic determinants controlling key seed nutritional phenotypes and to the characterization of their impact on grain nutritional value in pearl millet. PMID:29856884
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Thyroid endocrine disruption and external body morphology of Zebrafish
Sharma, Prakash; Grabowski, Timothy B.; Patino, Reynaldo
2016-01-01
This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15 mM)], combination of MZ (0.15 mM) and thyroxine (T4, 2 nM), T4 (2 nM), or control (reconstituted water) treatments until 33 dpf and subsequently maintained in reconstituted water until 45 dpf. Samples were taken at 33 and 45 dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45 dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45 dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45 dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45 dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45 dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Thienpont, Benedicte; Barata, Carlos; Raldúa, Demetrio, E-mail: drpqam@cid.csic.es
2013-06-01
Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable alternative model for screening chemicals impairing the thyroid hormone synthesis. The present study usedmore » the intrafollicular T4-content (IT4C) of zebrafish eleutheroembryos as integrative endpoint for testing the hypotheses that the effect of mixtures of TGFDs with a similar mode of action [inhibition of thyroid peroxidase (TPO)] was well predicted by a concentration addition concept (CA) model, whereas the response addition concept (RA) model predicted better the effect of dissimilarly acting binary mixtures of TGFDs [TPO-inhibitors and sodium-iodide symporter (NIS)-inhibitors]. However, CA model provided better prediction of joint effects than RA in five out of the six tested mixtures. The exception being the mixture MMI (TPO-inhibitor)-KClO{sub 4} (NIS-inhibitor) dosed at a fixed ratio of EC{sub 10} that provided similar CA and RA predictions and hence it was difficult to get any conclusive result. There results support the phenomenological similarity criterion stating that the concept of concentration addition could be extended to mixture constituents having common apical endpoints or common adverse outcomes. - Highlights: • Potential synergic or additive effect of mixtures of chemicals on thyroid function. • Zebrafish as alternative model for testing the effect of mixtures of goitrogens. • Concentration addition seems to predict better the effect of mixtures of goitrogens.« less
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Thyroid endocrine disruption and external body morphology of Zebrafish.
Sharma, Prakash; Grabowski, Timothy B; Patiño, Reynaldo
2016-01-15
This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15mM)], combination of MZ (0.15mM) and thyroxine (T4, 2nM), T4 (2nM), or control (reconstituted water) treatments until 33dpf and subsequently maintained in reconstituted water until 45dpf. Samples were taken at 33 and 45dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects. Published by Elsevier Inc.
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Das, S C; Isichei, U P; Egbuta, J O; Banwo, A I
1989-10-01
The prevalence of endemic goitre in Plateau State, Nigeria was established and an attempt was made to identify some of the possible environmental goitrogenic agents in the region to establish their likely relationship with the goitre endemicity. Iodine deficiency appears to be a major aetiological factor for the disease as indicated by low iodine levels observed in portable drinking water and in daily urinary excretion. The carbonate (CO3-) content of drinking water supply was found to bear a significant positive correlation with the goitre rate for the entire state (p less than 0.005). The calcium (Ca++) and magnesium (Mg++) levels of the drinking water also exhibited relatively good linear direct correlations with the percentage goitre distribution in a region, nearly 2/3 of the state. It is concluded that there is possibly an interplay of several factors and in particular the carbonate content of drinking water which, in association with a state of iodine deficiency, may be regarded as responsible for the goitre endemic seen in this part of the Continental Africa.
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Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.
Kero, Jukka; Ahmed, Kashan; Wettschureck, Nina; Tunaru, Sorin; Wintermantel, Tim; Greiner, Erich; Schütz, Günther; Offermanns, Stefan
2007-09-01
The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.
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Intoxication by Cyanide in Pregnant Sows: Prenatal and Postnatal Evaluation
Gotardo, André T.; Hueza, Isis M.; Manzano, Helena; Maruo, Viviane M.; Maiorka, Paulo C.; Górniak, Silvana L.
2015-01-01
Cyanide is a ubiquitous chemical in the environment and has been associated with many intoxication episodes; however, little is known about its potentially toxic effects on development. The aim of this study was to evaluate the effects of maternal exposure to potassium cyanide (KCN) during pregnancy on both sows and their offspring. Twenty-four pregnant sows were allocated into four groups that orally received different doses of KCN (0.0, 2.0, 4.0, and 6.0 mg/kg of body weight) from day 21 of pregnancy to term. The KCN-treated sows showed histological lesions in the CNS, thyroid follicle enlargement, thyroid epithelial thickening, colloid reabsorption changes, and vacuolar degeneration of the renal tubular epithelium. Sows treated with 4.0 mg/kg KCN showed an increase in the number of dead piglets at birth. Weaned piglets from all KCN-treated groups showed histological lesions in the thyroid glands with features similar to those found in their mothers. The exposure of pregnant sows to cyanide thus caused toxic effects in both mothers and piglets. We suggest that swine can serve as a useful animal model to assess the neurological, goitrogenic, and reproductive effects of cyanide toxicosis. PMID:26101526
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Worldwide prevalence and risk factors for feline hyperthyroidism: A review.
McLean, Joanne L; Lobetti, Remo G; Schoeman, Johan P
2014-11-14
Since first reported in the late 1970s, there has been a steady but dramatic increase in the worldwide prevalence of hyperthyroidism in cats. It is now regarded as the most common feline endocrine disorder, with diabetes mellitus coming a close second. Not only is there evidence for an increased worldwide prevalence of feline hyperthyroidism, but also for geographical variation in the prevalence of the disease. Despite its frequency, the underlying cause(s) of this common disease is or are not known, and therefore prevention of the disease is not possible. Due to the multiple risk factors that have been described for feline hyperthyroidism, however, it is likely that more than one factor is involved in its pathogenesis. Continuous, lifelong exposure to environmental thyroid-disruptor chemicals or goitrogens in food or water, acting together or in an additive fashion, may lead to euthyroid goitre and ultimately to autonomous adenomatous hyperplasia, thyroid adenoma and hyperthyroidism. This review aims to summarise the available published evidence for the changes observed in the worldwide prevalence of the disease, as well as risk factors that may contribute to development of hyperthyroidism in susceptible cats.
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Polyakova, V S; Sizova, Ye A; Miroshnikov, S A; Notova, S V; Zavaleyeva, S M
2015-01-01
The study was conducted on 15 male Wistar rats, which were injected intramuscularly with copper nanoparticle lyosols at a dose of 2.0 mg/kg body weight once a week for 3 months. Thyroid gland was removed 7 days after the last injection and was studied using histological, morphometric and immunohistochemical methods (demonstration of Ki-67 and caspase-3). Animals of the control group (n = 15) were administered distilled water at the same time intervals. It was found that after 1, 2, 3 and 4 injections of copper nanoparticles, the thyroid gland contained an increased number of large cyst-like follicles, while the average thyrocyte height of and the volume of their nuclei were reduced, which indicate a decline in hormone production. After 12 injections of copper nanoparticles, the hyperplastic thyroid gland demonstrated small follicles lined with columnar epithelium, which contained no or small amount of the colloid. The number of mitotically dividing thyrocytes was increased. Parafollicular cells demonstrated an apoptotic dominant. Morphological data suggest goitrogenic effect of multiple doses of copper nanopartides. The data received indicating the readiness of the thyroid cells to the programmed death and its possible depression (absence of signs of thyrocyte apoptosis) at different stages of the experiment confirm the modulating effect of copper on apoptosis.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ji, Cheng; Graduate University of Chinese Academy of Sciences, Beijing; Jin, Xia
Accumulating evidence indicates that a wide range of chemicals have the ability to interfere with the hypothalamic–pituitary–thyroid (HPT) axis. Novel endpoints should be evaluated in addition to existing methods in order to effectively assess the effects of these chemicals on the HPT axis. Thyroid-stimulating hormone subunit β (TSHβ) plays central regulatory roles in the HPT system. We identified the regulatory region that determines the expression level of zebrafish TSHβ in the anterior pituitary. In the transgenic zebrafish with EGFP driven by the TSHβ promoter, the similar responsive patterns between the expression levels of TSHβ:EGFP and endogenous TSHβ mRNA in themore » pituitary are observed following treatments with goitrogen chemicals and exogenous thyroid hormones (THs). These results suggest that the TSHβ:EGFP transgenic reporter zebrafish may be a useful alternative in vivo model for the assessment of chemicals interfering with the HPT system. Highlights: ► The promoter of zebrafish TSHβ gene has been identified. ► The stable TSHβ:EGFP transgenic zebrafish reporter germline has been generated. ► The EGFP in the transgenic fish recapitulated the pattern of pituitary TSHβ mRNA. ► The transgenic zebrafish may be an in vivo model for EDC assessment.« less
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Dehdari, Sahar; Hajimehdipoor, Homa
2018-02-01
Adiantum capillus-veneris Linn (Maidenhair fern) is an herb belonging to the family Pteridaceae. It is named as " Pare-siavashan " in medical and pharmaceutical textbooks of Iranian Traditional Medicine. The fronds of Maidenhair fern were mainly administrated by ancient physicians as single medicine or in combination with other plants in multi-herbal formulations for curing different diseases. Because of different chemical compositions, the herb fronds were also assessed for its numerous pharmacological effects. Therefore, the current study was done to review the traditional usage and modern pharmacological and toxicological effects of Maidenhair fern. Scientific databases and publications including Web of Science, PubMed, Scopus, Science direct, Cochrane Library, SID (for Persian papers) and medical and pharmaceutical textbooks of traditional medicine as well were searched for " Adiantum capillus-veneris ", " Maidenhair fern " and " Pare-siavashan " without limitation up to 2016. Maidenhair fern exhibited to possess anti-diabetic, anticonvulsant, analgesic, hypocholesterolemic, goitrogenic, anti-thyroidal, antibacterial, antifungal, wound healing, antiobesity, anti hair loss, anti-asthmatic, anti-inflammatory, antidiarrheal and antispasmodic, antioxidant as well as diuretic, anti-urolithiatic and detoxifying effects in modern medicine. Ancient physicians declared some of the confirmed pharmacological effects. Maidenhair fern frond can be a good candidate for clinical purpose. Therefore, future researches on the other mentioned effects in traditional medicine are recommended.
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Resveratrol has anti-thyroid effects both in vitro and in vivo.
Giuliani, Cesidio; Iezzi, Manuela; Ciolli, Laura; Hysi, Alba; Bucci, Ines; Di Santo, Serena; Rossi, Cosmo; Zucchelli, Mirco; Napolitano, Giorgio
2017-09-01
Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 μM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses. Copyright © 2017 Elsevier Ltd. All rights reserved.
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DEHDARI, Sahar; HAJIMEHDIPOOR, Homa
2018-01-01
Background: Adiantum capillus-veneris Linn (Maidenhair fern) is an herb belonging to the family Pteridaceae. It is named as “Pare-siavashan” in medical and pharmaceutical textbooks of Iranian Traditional Medicine. The fronds of Maidenhair fern were mainly administrated by ancient physicians as single medicine or in combination with other plants in multi-herbal formulations for curing different diseases. Because of different chemical compositions, the herb fronds were also assessed for its numerous pharmacological effects. Therefore, the current study was done to review the traditional usage and modern pharmacological and toxicological effects of Maidenhair fern. Methods: Scientific databases and publications including Web of Science, PubMed, Scopus, Science direct, Cochrane Library, SID (for Persian papers) and medical and pharmaceutical textbooks of traditional medicine as well were searched for “Adiantum capillus-veneris”, “Maidenhair fern” and “Pare-siavashan” without limitation up to 2016. Results: Maidenhair fern exhibited to possess anti-diabetic, anticonvulsant, analgesic, hypocholesterolemic, goitrogenic, anti-thyroidal, antibacterial, antifungal, wound healing, antiobesity, anti hair loss, anti-asthmatic, anti-inflammatory, antidiarrheal and antispasmodic, antioxidant as well as diuretic, anti-urolithiatic and detoxifying effects in modern medicine. Ancient physicians declared some of the confirmed pharmacological effects. Conclusion: Maidenhair fern frond can be a good candidate for clinical purpose. Therefore, future researches on the other mentioned effects in traditional medicine are recommended. PMID:29445628
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Heyland, Andreas; Reitzel, Adam M; Price, David A; Moroz, Leonid L
2006-01-01
Critical roles of hormones in metamorphic life history transitions are well documented in amphibians, lampreys, insects, and many plant species. Recent evidence suggests that thyroid hormones (TH) or TH-like compounds can regulate development to metamorphosis in echinoids (sea urchins, sand dollars, and their relatives). Moreover, previous research has provided evidence for endogenous hormone synthesis in both feeding and nonfeeding echinoderm larvae. However, the mechanisms for endogenous synthesis remain largely unknown. Here, we show that facultatively planktotrophic larvae (larvae that reach metamorphosis in the absence of food but have the ability to feed) from the subtropical sea biscuit Clypeaster rosaceus can synthesize thyroxine endogenously from incorporated iodine (I(125)). When treated with the goitrogen thiourea (a peroxidase inhibitor), iodine incorporation, thyroxine synthesis, and metamorphosis are all blocked in a dose-dependent manner. The inhibitory effect on metamorphosis can be rescued by administration of exogenous thyroxine. Finally, we demonstrate that thiourea induces morphological changes in feeding structures comparable to the phenotypic plastic response of larval structures to low food conditions, further supporting a signaling role of thyroxine in regulating larval morphogenesis and phenotypic plasticity. We conclude that upregulation of endogenous hormone synthesis might have been associated with the evolution of nonfeeding development, subsequently leading to morphological changes characteristic of nonfeeding development.
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Heyland, Andreas; Reitzel, Adam M.; Price, David A.; Moroz, Leonid L.
2014-01-01
SUMMARY Critical roles of hormones in metamorphic life history transitions are well documented in amphibians, lampreys, insects, and many plant species. Recent evidence suggests that thyroid hormones (TH) or TH-like compounds can regulate development to metamorphosis in echinoids (sea urchins, sand dollars, and their relatives). Moreover, previous research has provided evidence for endogenous hormone synthesis in both feeding and nonfeeding echinoderm larvae. However, the mechanisms for endogenous synthesis remain largely unknown. Here, we show that facultatively planktotrophic larvae (larvae that reach metamorphosis in the absence of food but have the ability to feed) from the subtropical sea biscuit Clypeaster rosaceus can synthesize thyroxine endogenously from incorporated iodine (I125). When treated with the goitrogen thiourea (a peroxidase inhibitor), iodine incorporation, thyroxine synthesis, and metamorphosis are all blocked in a dose-dependent manner. The inhibitory effect on metamorphosis can be rescued by administration of exogenous thyroxine. Finally, we demonstrate that thiourea induces morphological changes in feeding structures comparable to the phenotypic plastic response of larval structures to low food conditions, further supporting a signaling role of thyroxine in regulating larval morphogenesis and phenotypic plasticity. We conclude that upregulation of endogenous hormone synthesis might have been associated with the evolution of nonfeeding development, subsequently leading to morphological changes characteristic of nonfeeding development. PMID:17073939
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Which sources of flavonoids: complex diets or dietary supplements?
Egert, Sarah; Rimbach, Gerald
2011-01-01
There is increasing interest in the potential health benefits of dietary flavonoids. Fruits and vegetables, tea, and cocoa are rich natural sources of flavonoids. Epidemiological studies have indicated that consumption of these foods is likely to be associated with a reduced risk of cardiovascular disease, but the etiology of this benefit is not yet clearly defined. Furthermore, in some acute interventions, a positive effect of tea and cocoa on vascular function has been reported. An alternative source of flavonoids is dietary supplements, which have become increasingly popular in the recent past. In this context, it needs to be critically evaluated whether vascular health-promoting and other positive properties of flavonoid-rich diets can be replaced by purified flavonoids as dietary supplements. Plant sources of flavonoids contain a complex mixture of secondary plant metabolites and not only flavonoids per se. This complex mixture of secondary plant metabolites cannot be simply exchanged by single purified compounds as dietary supplements. If flavonoids are given as dietary supplements, toxicity issues as well as nutrient drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities. In this review article, the available literature on the safety issues surrounding high dose supplemental flavonoid consumption has been summarized.
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Which Sources of Flavonoids: Complex Diets or Dietary Supplements?1
Egert, Sarah; Rimbach, Gerald
2011-01-01
There is increasing interest in the potential health benefits of dietary flavonoids. Fruits and vegetables, tea, and cocoa are rich natural sources of flavonoids. Epidemiological studies have indicated that consumption of these foods is likely to be associated with a reduced risk of cardiovascular disease, but the etiology of this benefit is not yet clearly defined. Furthermore, in some acute interventions, a positive effect of tea and cocoa on vascular function has been reported. An alternative source of flavonoids is dietary supplements, which have become increasingly popular in the recent past. In this context, it needs to be critically evaluated whether vascular health-promoting and other positive properties of flavonoid-rich diets can be replaced by purified flavonoids as dietary supplements. Plant sources of flavonoids contain a complex mixture of secondary plant metabolites and not only flavonoids per se. This complex mixture of secondary plant metabolites cannot be simply exchanged by single purified compounds as dietary supplements. If flavonoids are given as dietary supplements, toxicity issues as well as nutrient drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities. In this review article, the available literature on the safety issues surrounding high dose supplemental flavonoid consumption has been summarized. PMID:22211185
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Hsu, Ping-Chi; Guo, Yueliang Leon; Li, Mei-Hui
2004-02-01
Polychlorinated biphenyls (PCBs) are considered potential endocrine disruptors due to their ability to act as estrogens, antiestrogens and goitrogens. The aim of this study is to ascertain whether acute postnatal treatment with 3,3',4,4'-tetrachlorobiphenyl (CB 77) affects sperm function and hormone levels in adult rats. Male Sprague-Dawley rats received CB 77 by ip injection of 2 or 20 mg/kg at day 21 and sacrificed at day 112. At day 112, right and left testis weights were significantly increased, whereas sperm count, motility, total motile sperm count, curvilinear velocity, average path velocity, straight-line velocity, and beat-cross frequency for motile sperm were significantly decreased in rats treated with 20 mg/kg CB 77. Sperm-oocyte penetration rate was significantly reduced in rats treated with either 2 or 20 mg/kg CB 77. There was high sperm acrosome reaction rate (ARR) in the 20 mg/kg CB 77-treated rats. There was a significant increase in thyroid-stimulating hormone level in the 20 mg/kg CB 77 group. However, no changes were seen in serum testosterone, thyroid hormones, or prolactin concentrations at day 112. In summary, this study showed that postnatal exposure to CB 77 might affect spermatogenesis, motility, ARR, and ability of fertilizing oocytes in mature rats. These results suggest that the sperm functions may be more susceptible or adapt less readily than the thyroid functions to endocrine disruption caused by dioxin-like PCB congeners.
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Do Thyroxine and Thyroid-Stimulating Hormone Levels Reflect Urinary Iodine Concentrations?
Soldin, Offie P.; Tractenberg, Rochelle E.; Pezzullo, John C.
2013-01-01
The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an ‘‘iodine-sufficient population.’’ Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988–1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15–44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status. PMID:15795649
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Martínez-Galán, J R; Pedraza, P; Santacana, M; Escobar del Ray, F; Morreale de Escobar, G; Ruiz-Marcos, A
1997-01-01
The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role. PMID:9169500
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Animal models of disease: feline hyperthyroidism: an animal model for toxic nodular goiter.
Peterson, Mark E
2014-11-01
Since first discovered just 35 years ago, the incidence of spontaneous feline hyperthyroidism has increased dramatically to the extent that it is now one of the most common disorders seen in middle-aged to senior domestic cats. Hyperthyroid cat goiters contain single or multiple autonomously (i.e. TSH-independent) functioning and growing thyroid nodules. Thus, hyperthyroidism in cats is clinically and histologically similar to toxic nodular goiter in humans. The disease in cats is mechanistically different from Graves' disease, because neither the hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells, but iodine deficiency, other nutritional goitrogens, or environmental disruptors may play a role in the disease pathogenesis. Clinical features of feline toxic nodular goiter include one or more palpable thyroid nodules, together with signs of hyperthyroidism (e.g. weight loss despite an increased appetite). Diagnosis of feline hyperthyroidism is confirmed by finding the increased serum concentrations of thyroxine and triiodothyronine, undetectable serum TSH concentrations, or increased thyroid uptake of radioiodine. Thyroid scintigraphy demonstrates a heterogeneous pattern of increased radionuclide uptake, most commonly into both thyroid lobes. Treatment options for toxic nodular goiter in cats are similar to that used in humans and include surgical thyroidectomy, radioiodine, and antithyroid drugs. Most authorities agree that ablative therapy with radioiodine is the treatment of choice for most cats with toxic nodular goiter, because the animals are older, and the disease will never go into remission. © 2014 Society for Endocrinology.
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Hu, Fang; Knoedler, Joseph R.
2016-01-01
Thyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs. PMID:26886257
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Drifting continents and endemic goitre in northern Pakistan.
Stewart, A G
1990-01-01
Although Baltistan, north east Pakistan, is in a region of iodine deficiency disorders, the distribution of goitre within the district, according to age and sex, has not been clearly defined. To establish the prevalence of the condition and to measure the reported difference in prevalence in the north and south of the district thyroid size was assessed in new patients attending the Aman clinic, Khapalu, and outlying areas between April and September from 1981 to 1986. Samples of potable water collected from villages were analysed for iodine (as iodide) concentrations in Britain. Population weighted prevalences were: in the north in males 20.4%, in females 28.1% and in the south in males 13.9%, in females 21.2%. There was an overall deficiency of iodine in the water (mean iodine (as iodide) concentrations (north) 11.0 nmol/l (1.4 micrograms/l), (south) 11.8 nmol/l (1.5 micrograms/l) (95% confidence interval -0.7 to 0.9). The differences followed the Main Karakoram Thrust, suggesting a geological goitrogen in the north, which might be minerals containing ions such as BF4- and SO3F-, and molybdenite and calcium, which are present in rocks in Baltistan. A new hypothesis for the genesis of endemic goitre is proposed--that is, that continents on crustal plates drift across the earth and collide, one plate sliding under the other and melting, giving rise to characteristic mineral assemblages in the overlying rocks. As the minerals weather out they enter the diet of the local population, where in the presence of iodine deficiency they produce or enhance iodine deficiency disorders. Despite the current iodised oil campaign by the Pakistani government with Unicef a long term working iodisation programme is still urgently needed. PMID:2372605
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Drifting continents and endemic goitre in northern Pakistan.
Stewart, A G
1990-06-09
Although Baltistan, north east Pakistan, is in a region of iodine deficiency disorders, the distribution of goitre within the district, according to age and sex, has not been clearly defined. To establish the prevalence of the condition and to measure the reported difference in prevalence in the north and south of the district thyroid size was assessed in new patients attending the Aman clinic, Khapalu, and outlying areas between April and September from 1981 to 1986. Samples of potable water collected from villages were analysed for iodine (as iodide) concentrations in Britain. Population weighted prevalences were: in the north in males 20.4%, in females 28.1% and in the south in males 13.9%, in females 21.2%. There was an overall deficiency of iodine in the water (mean iodine (as iodide) concentrations (north) 11.0 nmol/l (1.4 micrograms/l), (south) 11.8 nmol/l (1.5 micrograms/l) (95% confidence interval -0.7 to 0.9). The differences followed the Main Karakoram Thrust, suggesting a geological goitrogen in the north, which might be minerals containing ions such as BF4- and SO3F-, and molybdenite and calcium, which are present in rocks in Baltistan. A new hypothesis for the genesis of endemic goitre is proposed--that is, that continents on crustal plates drift across the earth and collide, one plate sliding under the other and melting, giving rise to characteristic mineral assemblages in the overlying rocks. As the minerals weather out they enter the diet of the local population, where in the presence of iodine deficiency they produce or enhance iodine deficiency disorders. Despite the current iodised oil campaign by the Pakistani government with Unicef a long term working iodisation programme is still urgently needed.
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Izaguirre, M F; García-Sancho, M N; Miranda, L A; Tomas, J; Casco, V H
2008-08-01
Cell adhesion molecules act as signal transducers from the extracellular environment to the cytoskeleton and the nucleus and consequently induce changes in the expression pattern of structural proteins. In this study, we showed the effect of thyroid hormone (TH) inhibition and arrest of metamorphosis on the expression of E-cadherin, beta-and alpha-catenin in the developing kidney of Bufo arenarum. Cell adhesion molecules have selective temporal and spatial expression during development suggesting a specific role in nephrogenesis. In order to study mechanisms controlling the expression of adhesion molecules during renal development, we blocked the B. arenarum metamorphosis with a goitrogenic substance that blocks TH synthesis. E-cadherin expression in the proximal tubules is independent of thyroid control. However, the blockage of TH synthesis causes up-regulation of E-cadherin in the collecting ducts, the distal tubules and the glomeruli. The expression of beta-and alpha-catenin in the collecting ducts, the distal tubules, the glomeruli and the mesonephric mesenchyme is independent of TH. TH blockage causes up-regulation of beta-and alpha-catenin in the proximal tubules. In contrast to E-cadherin, the expression of the desmosomal cadherin desmoglein 1 (Dsg-1) is absent in the control of the larvae kidney during metamorphosis and is expressed in some interstitial cells in the KClO4 treated larvae. According to this work, the Dsg-1 expression is down-regulated by TH. We demonstrated that the expression of E-cadherin, Dsg-1, beta-catenin and alpha-catenin are differentially affected by TH levels, suggesting a hormone-dependent role of these proteins in the B. arenarum renal metamorphosis.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Meserve, L.A.; Murray, B.A.; Landis, J.A.
1992-05-01
The organohalides polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) remain troublesome environmental pollutants. For example, the percentage of the population in which PCB is detectable in adipose tissue remains high. These compounds are of particular interest to residents of the North Central United States, especially in regions surrounding the Great Lakes where contaminated fish may be a regular component of the diet. Additionally, PBB was mistakenly fed to cattle and chickens in Michigan during the early 1970s, products of which were ingested by humans. Among the physiological effects of ingestion of PCB or PBB is the depression of thyroid status,more » which has been reported in adult humans, in adult experimental animals, and in the offspring of these animals. In adult rats, circulating levels of thyroid hormones are inversely proportional to dose of PCB or PBB in the diet. On the other hand, reports of effects of these organohalides on adrenocortical function remain equivocal, describing both PCB- and PBB-induced depression, and absence of effect in rats and monkeys. Despite the possible consequences of maternal ingestion of PCB or PBB on future generations, little work has been done previously to determine whether consumption of these materials by pregnant and lactating animals confers hypothyroidism on their offspring, and/or influences other mechanisms of endocrine control in the young. Since early studies showed that hypothyroidism induced by feeding pregnant rats the goitrogen thiouracil altered the functional capabilities in their young of the hypothalamus-pituitary-adrenal (HPA) axis, as revealed by circulating corticosterone levels, the present study was done to determine whether ingestion of either PCB (Aroclor 1254[reg sign]) or PBB (FireMaster BP-6[reg sign]) by pregnant and lactating rats resulted in depressed thyroid status and/or modified HPA axis function in their 15 day old young. 19 refs., 1 fig., 1 tab.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
De Gregorio, Francesca; Pellegrino, Mario; Picchietti, Simona
2011-06-01
DDT is a highly lipophilic molecule known to deplete membrane rafts of their phosphoglycolipid and cholesterol contents. However, we have recently shown that DDT can also alter the thyroid homeostasis by inhibiting TSH receptor (TSHr) internalization. The present study was undertaken to verify whether DDT goitrogenic effects are due to the insecticide acting directly on TSHr or via alteration of the membrane rafts hosting the receptor itself. Our results demonstrate that, in CHO-TSHr transfected cells, TSHr is activated in the presence of TSH, while it is inhibited following DDT exposure. DDT can also reduce the endocytic vesicular traffic, alter themore » extension of multi-branched microvilli along their plasma membranes and induce TSHr shedding in vesicular forms. To verify whether TSHr displacement might depend on DDT altering the raft constitution of CHO-TSHr cell membranes the extent of TSHr and lipid raft co-localization was examined by confocal microscopy. Evidence shows that receptor/raft co-localization increased significantly upon exposure to TSH, while receptors and lipid rafts become dislodged on opposite cell poles in DDT-exposed CHO-TSHr cells. As a control, under similar culturing conditions, diphenylethylene, which is known to be a lipophilic substance that is structurally related to DDT, did not affect the extent of TSHr and lipid raft co-localization in CHO-TSHr cells treated with TSH. These findings corroborate and extend our view that, in CHO cells, the DDT disrupting action on TSHr is primarily due to the insecticide acting on membranes to deplete their raft cholesterol content, and that the resulting inhibition on TSHr internalization is due to receptor dislodgement from altered raft microdomains of the plasma membrane. - Highlights: >DDT is a pesticide with a severe environmental impact >Epidemiologic correlation exists between exposition to DDT and thyroid dysfunction >DDT is a lipophilic molecule that has been shown to inhibit TSH receptor function >DDT depletes membrane raft cholesterol content and by this way inhibits TSH receptor« less
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Manzon, Lori A; Youson, John H; Holzer, Guillaume; Staiano, Leopoldo; Laudet, Vincent; Manzon, Richard G
2014-08-01
Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRα/β split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRβ and TRα, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR expression data suggests that THs, either directly or via a metabolite, may function to positively modulate changes at the tissue or organ levels during lamprey metamorphosis. Collectively the results presented herein support the hypothesis that THs have a dual functional role in the lamprey life cycle whereby high levels promote larval feeding, growth and lipogenesis and low levels promote metamorphosis. Copyright © 2014 Elsevier Inc. All rights reserved.
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Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail
2012-11-01
The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby influencing the functional development of this major sensory and motor structure. However, the neurochemical development of glia and other non-neuronal cells, where BuChE is mainly localized, is comparatively unaffected in these abnormal developmental conditions. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.
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Spring, S R; Bastian, T W; Wang, Y; Kosian, P; Anderson, G W; Gilbert, M E
2016-01-01
Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly support previous work indicating prenatal TH insufficiency but not postnatal TH insufficiency in offspring is required for SBH formation. Published by Elsevier Inc.
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Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis.
Hard, G C
1998-01-01
This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation. PMID:9681969