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Masao Hirose - One of the best experts on this subject based on the ideXlab platform.
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lack of effect of soy isoflavone on Thyroid Hyperplasia in rats receiving an iodine deficient diet
Japanese Journal of Cancer Research, 2001Co-Authors: Hwa-young Son, Akiyoshi Nishikawa, Takako Ikeda, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of Thyroid Hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum Thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or Hyperplasia of Thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.
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Lack of Effect of Soy Isoflavone on Thyroid Hyperplasia in Rats Receiving an Iodine‐deficient Diet
Japanese Journal of Cancer Research, 2001Co-Authors: Hwa-young Son, Akiyoshi Nishikawa, Takako Ikeda, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of Thyroid Hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum Thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or Hyperplasia of Thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.
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dramatic synergism between excess soybean intake and iodine deficiency on the development of rat Thyroid Hyperplasia
Carcinogenesis, 2000Co-Authors: Takako Ikeda, Akiyoshi Nishikawa, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:The effects of defatted soybean and/or iodine-deficient diet feeding were investigated in female F344 rats. Rats were divided into four groups, each consisting of 10 animals, and fed basal AIN-93G diet in which the protein was exchanged for 20% gluten (Group 1), iodine-deficient gluten (Group 2), 20% defatted soybean (Group 3) and iodine-deficient defatted soybean (Group 4). At week 10, relative Thyroid gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 2 (15.5 +/- 1.3) and 4 (81.7 +/- 8.6) than in Group 1 (8.4 +/- 2.0) and pituitary gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 3 (9.1 +/- 0. 6) and 4 (9.7 +/- 1.5) than in Group 1 (6.5 +/- 1.5). Serum biochemical assays revealed thyroxine to be significantly (P < 0.05) lower in Groups 2 and 4 than in Group 1. On the other hand, serum Thyroid-stimulating hormone (TSH) was significantly (P < 0.01) higher in Groups 3 and 4 than in Group 1. This was particularly striking for TSH (ng/ml) at week 10 in Group 4 (126 +/- 11) as compared with Groups 1 (4.36 +/- 0.30), 2 (4.84 +/- 0.80) and 3 (5. 78 +/- 0.80). Histologically, marked diffuse follicular Hyperplasia of the Thyroid was evident in Group 4 rats. Proliferating cell nuclear antigen labeling indices (%) were significantly higher (P < 0.05) in Groups 2 (4.8 +/- 2.5) and 4 (13.2 +/- 1.1) than in Group 1 (0.4 +/- 0.5). Ultrastructurally, severe disorganization and disarrangement of mitochondria were apparent in Thyroid follicular cells of Group 4. In the anterior pituitary, dilated rough surfaced endoplasmic reticulum and increased secretory granules were remarkable in this group. Our results thus strongly suggest that dietary defatted soybean synergistically stimulates the growth of rat Thyroid with iodine deficiency, partly through a pituitary-dependent pathway.
Jacques Emile Dumont - One of the best experts on this subject based on the ideXlab platform.
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TSH Receptor Mutations and Thyroid Disease.
Trends in Endocrinology & Metabolism, 1998Co-Authors: Laurence Duprez, Jacques Emile Dumont, Gilbert Vassart, Jasmine Parma, P Rodien, Jacqueline Van Sande, M AbramowiczAbstract:Mutations of the thyrotropin receptor (TSHr) can be loss of function or gain of function. Loss-of-function mutations can affect a variety of loci in the TSHr gene. Their most common manifestation is resistance to TSH; they may also be the cause of a subset of cases of congenital hypoThyroidism. Gain-of-function mutations are of greater theoretical interest. Somatic mutations constitutively activating the TSHr are the major cause of benign toxic Thyroid adenomas, and of some cases of multinodular goiters. They underlie hereditary toxic Thyroid Hyperplasia, and have been found in cases of sporadic congenital non-autoimmune hyperThyroidism. A role for TSHr polymorphisms in Graves' disease has not been documented.
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Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic Thyroid Hyperplasia
Journal of Clinical Endocrinology & Metabolism, 1996Co-Authors: Massimo Tonacchera, J. Van Sande, Filomena Cetani, Stéphane Swillens, Claire Schvartz, P Winiszewski, L Portmann, Jacques Emile Dumont, Gilbert Vassart, Jasmine ParmaAbstract:We report three unrelated families in which hyperThyroidism associated with Thyroid Hyperplasia was transmitted in an autosomal dominant fashion, in the absence of signs of autoimmunity. Exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from DNA of peripheral leukocytes. In one family, a C to A transversion resulted in an S505R substitution in the third transmembrane segment; in the second, an A to T transversion caused a N650Y substitution in the sixth transmembrane segment; and in the third family, an A to G transition resulted in an N670S substitution in the seventh transmembrane segment. When expressed by transfection in COS-7 cells, each mutated receptor displayed an increase in constitutive stimulation of cAMP production; no effect on basal accumulation of inositol phosphates (IP) could be detected. In binding studies, cells transfected with wild-type or mutated receptors showed similar levels of expression, with the mutated receptors displaying similar or slightly increased affinity for bovine TSH (bTSH) binding. Cells transfected with S505R and N650Y mutants showed a similar cAMP maximal TSH-stimulated accumulation over the cells transfected with the wild type, whereas N670S transfectants showed a blunted response with an increase in EC50. A higher IP response to 100 mU/mL bTSH over that obtained with the wild-type receptor was obtained in cells transfected with N650Y; in contrast, cells transfected with S505R showed a blunted IP production (50% less), and the N670S mutant completely lost the ability to stimulate IP accumulation in response to bTSH. The differential effects of individual mutations on stimulation by bTSH of cAMP or IP accumulation suggest that individual mutant receptors may achieve different active conformations with selective abilities to couple to Gs alpha and to Gq alpha.
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germline mutations in the thyrotropin receptor gene cause non autoimmune autosomal dominant hyperThyroidism
Nature Genetics, 1994Co-Authors: Laurence Duprez, Claire Schvartz, Jasmine Parma, Jacqueline Van Sande, Anouk Allgeier, J Leclere, Mariejoelle Delisle, Marc Decoulx, J Orgiazzi, Jacques Emile DumontAbstract:The thyrotropin receptor (TSHR), a member of the large family of G protein–coupled receptors, controls both the function and growth of Thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non–autoimmune autosomal dominant hyperThyroidism (toxic Thyroid Hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS–7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning Thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated.
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Thyroid expression of an A2 adenosine receptor transgene induces Thyroid Hyperplasia and hyperThyroidism.
The EMBO Journal, 1992Co-Authors: Catherine Ledent, Jacques Emile Dumont, Gilbert Vassart, Marc ParmentierAbstract:Cyclic AMP (cAMP) is the major intracellular second messenger of thyrotropin (TSH) action on Thyroid cells. It stimulates growth as well as the function and differentiation of cultured thyrocytes. The adenosine A2 receptor, which activates adenylyl cyclase via coupling to the stimulating G protein (Gs), has been shown to promote constitutive activation of the cAMP cascade when transfected into various cell types. In order to test whether the A2 receptor was able to function similarly in vivo and to investigate the possible consequences of permanent adenylyl cyclase activation in Thyroid cells, lines of transgenic mice were generated expressing the canine A2 adenosine receptor under control of the bovine thyroglobulin gene promoter. Thyroid-specific expression of the A2 adenosine receptor transgene promoted gland Hyperplasia and severe hyperThyroidism causing premature death of the animals. The resulting goitre represents a model of hyperfunctioning adenomas: it demonstrates that constitutive activation of the cAMP cascade in such differentiated epithelial cells is sufficient to stimulate autonomous and uncontrolled function and growth.
Franco Mantero - One of the best experts on this subject based on the ideXlab platform.
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enhanced expression of transforming growth factor β1 in rat Thyroid Hyperplasia is thyrotropin induced and time dependent
European Journal of Endocrinology, 1996Co-Authors: P P Morosini, A Taccaliti, Giorgio Arnaldi, G Simonella, M D Petrelli, V Mancini, R Montironi, M Scarpelli, L Diamanti, Franco ManteroAbstract:Forty-three 8-week-old male Wistar rats were studied to evaluate temporal changes of transforming growth factor beta1, (TGF-beta1) mRNA levels in Thyroid tissue during pharmacologically induced goiter. Four rats were treated with purified bovine thyrotropin (TSH; Ambinon, 2 mU/day sc) for 7 days before being sacrificed. Thirty-one were treated with propylthiouracil (PTU), added to their drinking water at a concentration of 0.2 g%, and subsequently were sacrificed as follows: five after 1 week (PTU-1): five after 2 weeks (PTU-2); five after 4 weeks (PTU-4); five after 8 weeks (PTU-8); five after 12 weeks (PTU-12). In six rats, after 12 weeks of treatment. PTU was withdrawn for 2 months and subsequently started again in three rats which were sacrificed after 2 weeks (PTU-R); the remaining three rats were sacrificed without any further treatment (PTU-R control). Eight rats (control rats) were never treated and served as controls. After sacrifice, blood was drawn for determination of total thyroxine and the Thyroid was excised and subdivided into two lobes. Northern analysis for TGF-beta1 was performed in one lobe. while histological and immunohistochemical studies were performed in the other lobe. Gene expression of TGF-beta1 was induced in TSH- and PTU-treated rats. In TSH-treated rats TGF-beta1 gene expression was less detectable than in PTU-treated rats, where it became evident after 2 weeks and remained through weeks 4-8. Gene expression of TGF-beta1 wits also seen in PTU-R rats, but not in the control and in the PTU-R control. Immunohistochemical analysis showed a different presence and location for the TGF-beta1 protein, which appears to be dependent on the time of exposure to mitogenic stimulus. In conclusion, TGF-beta1 is produced in response to both a direct (TSH by itself) and indirect (TSH induced by PTU-induced hypoThyroidism) cellular proliferative stimulus and is not linked to an adaptative phenomenon secondary to hypoThyroidism. The immunohistochemical location of TGF-beta1 within the thyrocytes is influenced by mitogen exposure time. A TGF-beta1 immunohistochemical evaluation may be important to define exposure time and activity of goitrogenic stimuli.
Laurence Duprez - One of the best experts on this subject based on the ideXlab platform.
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TSH Receptor Mutations and Thyroid Disease.
Trends in Endocrinology & Metabolism, 1998Co-Authors: Laurence Duprez, Jacques Emile Dumont, Gilbert Vassart, Jasmine Parma, P Rodien, Jacqueline Van Sande, M AbramowiczAbstract:Mutations of the thyrotropin receptor (TSHr) can be loss of function or gain of function. Loss-of-function mutations can affect a variety of loci in the TSHr gene. Their most common manifestation is resistance to TSH; they may also be the cause of a subset of cases of congenital hypoThyroidism. Gain-of-function mutations are of greater theoretical interest. Somatic mutations constitutively activating the TSHr are the major cause of benign toxic Thyroid adenomas, and of some cases of multinodular goiters. They underlie hereditary toxic Thyroid Hyperplasia, and have been found in cases of sporadic congenital non-autoimmune hyperThyroidism. A role for TSHr polymorphisms in Graves' disease has not been documented.
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germline mutations in the thyrotropin receptor gene cause non autoimmune autosomal dominant hyperThyroidism
Nature Genetics, 1994Co-Authors: Laurence Duprez, Claire Schvartz, Jasmine Parma, Jacqueline Van Sande, Anouk Allgeier, J Leclere, Mariejoelle Delisle, Marc Decoulx, J Orgiazzi, Jacques Emile DumontAbstract:The thyrotropin receptor (TSHR), a member of the large family of G protein–coupled receptors, controls both the function and growth of Thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non–autoimmune autosomal dominant hyperThyroidism (toxic Thyroid Hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS–7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning Thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated.
Takako Ikeda - One of the best experts on this subject based on the ideXlab platform.
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lack of effect of soy isoflavone on Thyroid Hyperplasia in rats receiving an iodine deficient diet
Japanese Journal of Cancer Research, 2001Co-Authors: Hwa-young Son, Akiyoshi Nishikawa, Takako Ikeda, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of Thyroid Hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum Thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or Hyperplasia of Thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.
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Lack of Effect of Soy Isoflavone on Thyroid Hyperplasia in Rats Receiving an Iodine‐deficient Diet
Japanese Journal of Cancer Research, 2001Co-Authors: Hwa-young Son, Akiyoshi Nishikawa, Takako Ikeda, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:We have reported a dramatic synergism between soy intake and iodine deficiency regarding induction of Thyroid Hyperplasia in rats. Because isoflavones are active constituents of soybeans, in the present study, their possible contribution was examined. Female F344 rats were divided into 8 groups, exposed to diet containing a 0.2% soy isoflavone mixture (SI), 0.2% SI + iodine deficiency (ID), 0.04% SI, 0.04% SI + ID, 20% defatted soybean (DS) alone, 20% DS + ID, ID alone or basal diet alone for 5 weeks. Thyroid weight was not influenced by SI, but was increased by the ID and DS diets with a further significant increment in the DS + ID group (P < 0.01). Compared to the control value, serum T(4) was significantly (P < 0.01) increased by 20% DS alone and decreased in all groups given the ID treatment (P < 0.001). Serum Thyroid stimulating hormone (TSH) level was increased by ID, and further enhanced by DS (P < 0.01) but not SI. Histopathologically, diffuse hypertrophy and / or Hyperplasia of Thyroid follicles were observed in the ID-treated groups, the severity being enhanced by DS but not SI. Proliferating cell nuclear antigen labeling indices (%) were elevated in the ID diet groups and again enhanced by DS, but not SI. These results thus suggest that isoflavones may not be involved in the mechanisms underlying the synergistic goitrogenic effect of soybean with iodine deficiency.
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dramatic synergism between excess soybean intake and iodine deficiency on the development of rat Thyroid Hyperplasia
Carcinogenesis, 2000Co-Authors: Takako Ikeda, Akiyoshi Nishikawa, Takayoshi Imazawa, Shuichi Kimura, Masao HiroseAbstract:The effects of defatted soybean and/or iodine-deficient diet feeding were investigated in female F344 rats. Rats were divided into four groups, each consisting of 10 animals, and fed basal AIN-93G diet in which the protein was exchanged for 20% gluten (Group 1), iodine-deficient gluten (Group 2), 20% defatted soybean (Group 3) and iodine-deficient defatted soybean (Group 4). At week 10, relative Thyroid gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 2 (15.5 +/- 1.3) and 4 (81.7 +/- 8.6) than in Group 1 (8.4 +/- 2.0) and pituitary gland weights (mg/100 g body wt) were significantly (P < 0.01) higher in Groups 3 (9.1 +/- 0. 6) and 4 (9.7 +/- 1.5) than in Group 1 (6.5 +/- 1.5). Serum biochemical assays revealed thyroxine to be significantly (P < 0.05) lower in Groups 2 and 4 than in Group 1. On the other hand, serum Thyroid-stimulating hormone (TSH) was significantly (P < 0.01) higher in Groups 3 and 4 than in Group 1. This was particularly striking for TSH (ng/ml) at week 10 in Group 4 (126 +/- 11) as compared with Groups 1 (4.36 +/- 0.30), 2 (4.84 +/- 0.80) and 3 (5. 78 +/- 0.80). Histologically, marked diffuse follicular Hyperplasia of the Thyroid was evident in Group 4 rats. Proliferating cell nuclear antigen labeling indices (%) were significantly higher (P < 0.05) in Groups 2 (4.8 +/- 2.5) and 4 (13.2 +/- 1.1) than in Group 1 (0.4 +/- 0.5). Ultrastructurally, severe disorganization and disarrangement of mitochondria were apparent in Thyroid follicular cells of Group 4. In the anterior pituitary, dilated rough surfaced endoplasmic reticulum and increased secretory granules were remarkable in this group. Our results thus strongly suggest that dietary defatted soybean synergistically stimulates the growth of rat Thyroid with iodine deficiency, partly through a pituitary-dependent pathway.