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Samuel Refetoff - One of the best experts on this subject based on the ideXlab platform.
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Resistance to Thyroid Hormone: one of several defects causing reduced sensitivity to Thyroid Hormone.
Nature clinical practice. Endocrinology & metabolism, 2008Co-Authors: Samuel RefetoffAbstract:Resistance to Thyroid Hormone: one of several defects causing reduced sensitivity to Thyroid Hormone
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A case of resistance to Thyroid Hormone without mutation in the Thyroid Hormone receptor beta
Irish Journal of Medical Science, 2005Co-Authors: J. H. Mcdermott, A. M. Dumitrescu, D. Gasparro, Lothar Moeller, Amar Agha, Samuel Refetoff, M Mcmahon, Seamus SreenanAbstract:Background Resistance to Thyroid Hormone (RTH) is a condition caused by tissue hyposensitivity to the effects of circulating Thyroid Hormone, and may be misdiagnosed as hyperThyroidism. Aims We report the first case of RTH in an Irish patient highlighting the clinical features and the pathophysiological mechanism underlying the characteristic laboratory abnormalities found in the condition. Methods We describe an isolated case of RTH initially misdiagnosed as hyperThyroidism, and detail the investigations which ultimately led to the correct diagnosis. Genetic screening of the Thyroid Hormone receptor beta gene was performed. Results Thyroid function tests including T3 suppression test and TRH-stimulation test suggested a diagnosis of RTH. Genetic testing failed to demonstrate a mutation in the Thyroid Hormone receptor. Conclusion RTH is a rare inherited condition that may be misdiagnosed as hyperThyroidism. The case we describe most likely results from a de novo mutation in an as yet undiscovered gene. RTH should be considered in patients with elevated Thyroid Hormone levels and normal TSH so that unnecessary and potentially harmful treatment can be avoided.
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A case of Resistance to Thyroid Hormone without mutation in the Thyroid Hormone receptor beta.
Irish Journal of Medical Science, 2005Co-Authors: J. H. Mcdermott, A. M. Dumitrescu, D. Gasparro, Amar Agha, Samuel Refetoff, M Mcmahon, Lars C. Moeller, Seamus SreenanAbstract:Background Resistance to Thyroid Hormone (RTH) is a condition caused by tissue hyposensitivity to the effects of circulating Thyroid Hormone, and may be misdiagnosed as hyperThyroidism.
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Resistance to Thyroid Hormone in the Absence of Mutations in the Thyroid Hormone Receptor Genes
Current Opinion in Endocrinology & Diabetes, 2000Co-Authors: Samuel Refetoff, Peter M. Sadow, Joachim Pohlenz, Sirimon Reutrakul, Kimberly Dennis, Deborah Mannavola, Roy E. WeissAbstract:Resistance to Thyroid Hormone (RTH) is a syndrome of reduced tissue sensitivity to Thyroid Hormone. In the majority of subjects, RTH is caused by mutant Thyroid Hormone receptors (TR) s molecules that interfere with the function of the normal TRs, thus resulting in a dominant mode of inheritance. RTH caused by TRβ gene deletion, on the other hand, is inherited as a recessive trait. In as many as 15% of families, RTH manifests in the absence of a TR gene abnormality. The clinical manifestations and laboratory abnormalities in such subjects are not significantly different than those found in individuals with TRs defects. We propose that the molecular defect causing RTH without TR gene mutations must be elsewhere in the pathway of Thyroid Hormone action.
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Resistance to Thyroid Hormone Caused by a New Mutation (V336M) in the Thyroid Hormone Receptor β Gene
Thyroid, 1999Co-Authors: Joachim Pohlenz, W. Schönberger, Thomas Koffler, Samuel RefetoffAbstract:Resistance to Thyroid Hormone (RTH), usually caused by an inherited defect of the Thyroid Hormone receptor β (TRβ), results in a reduced responsiveness of target tissues to Thyroid Hormone. Until n...
Paul J Davis - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Hormone, PD-L1, and cancer
Journal of Cancer Research and Practice, 2019Co-Authors: Yi-ru Chen, Paul J Davis, Ya-jung Shih, Jaqueline Whang-peng, Hung-yun Lin, Kuan WangAbstract:Objective: Thyroid Hormone plays a vital role in maintaining whole-body physiological activities. However, several different disorders can arise when Thyroid Hormone is abnormal. Even more, Thyroid Hormone has been shown to stimulate cancer cell proliferation at physiological concentration. By binding to cell surface integrin αvβ3, Thyroid Hormone, especially thyroxine activates ERK1/2 activation and sequentially stimulates cell proliferation. Different mechanisms have been demonstrated to be involved in thyroxine-induced cancer proliferation. Checkpoint, PD-1/PD-L1, has shown highly correlated to cancer proliferation and survival. Data Sources: We examined actions of thyroxine and Nano-diamino-tetrac (NDAT; Nanotetrac) on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in various cancer cells. Methodologies used are qPCR, Western blot analyses, confocal microscopy, and xenograft. Study Selection: We investigate mechanisms involved in Thyroid Hormone-induced PD-L1 expression and inhibitory effect of NDAT on Thyroid Hormone-induced PD-L1 expression. Either blocking Thyroid Hormone-binding on integrin αvβ3 or using NDAT can inhibit PD-L1 expression. Results: Our studies indicate that Thyroid Hormone induces PD-L1 expression via activating ERK1/2, PI3K, and STAT3 in different types of cancer cells. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. Other studies on PubMed also indicate thyroxine's actions are via integrin αvβ3. Conclusions: Thyroid Hormone-induced PD-L1 expression not only facilitates cancer cell proliferation but also interferes with chemotherapy. In this current review, we will discuss mechanisms involved in Thyroid Hormone-induced PD-L1 expression. In addition, role of PD-L1 in Thyroid Hormone-induced cancer growth and metastasis will be addressed.
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nongenomic actions of Thyroid Hormone
Nature Reviews Endocrinology, 2016Co-Authors: Paul J Davis, Fernando Goglia, Jack L LeonardAbstract:This Review outlines the molecular basis of nongenomic mechanisms of Thyroid Hormone action. Davis and colleagues also discuss the possible physiological or pathophysiological consequences of these actions, as well as the interactions between nongenomic and genomic effects of Thyroid Hormone.
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Promotion by Thyroid Hormone of cytoplasm-to-nucleus shuttling of Thyroid Hormone receptors.
Steroids, 2008Co-Authors: Paul J Davis, Faith B DavisAbstract:Abstract Confocal microscopy and cell fractionation studies have revealed the residence of nuclear Thyroid Hormone receptors (TR) in cytoplasm. Treatment of cells with the Hormone ( l -thyroxine or 3,5,3′-triiodo- l -thyronine, T 3 ) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRβ1 isoform may be found in cytoplasm of Thyroid Hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRα1 is also increased by T 3 . It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid Hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for Thyroid Hormone on integrin αvβ3 that does not share homologies with TR may move to the cell nucleus in Thyroid Hormone-treated cells. Because cells in the intact organism are tonically exposed to Thyroid Hormone, the latter is likely to contribute to the basal rate of nuclear import of Thyroid Hormone receptors.
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Promotion by Thyroid Hormone of cytoplasm-to-nucleus shuttling of Thyroid Hormone receptors.
Steroids, 2008Co-Authors: Paul J Davis, Faith B DavisAbstract:Confocal microscopy and cell fractionation studies have revealed the residence of nuclear Thyroid Hormone receptors (TR) in cytoplasm. Treatment of cells with the Hormone (L-thyroxine or 3,5,3'-triiodo-L-thyronine, T(3)) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRbeta1 isoform may be found in cytoplasm of Thyroid Hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRalpha1 is also increased by T(3). It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid Hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for Thyroid Hormone on integrin alphavbeta3 that does not share homologies with TR may move to the cell nucleus in Thyroid Hormone-treated cells. Because cells in the intact organism are tonically exposed to Thyroid Hormone, the latter is likely to contribute to the basal rate of nuclear import of Thyroid Hormone receptors.
Roy E. Weiss - One of the best experts on this subject based on the ideXlab platform.
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Specificity of Thyroid Hormone receptor subtype and steroid receptor coactivator-1 on Thyroid Hormone action
American Journal of Physiology-endocrinology and Metabolism, 2002Co-Authors: Peter M. Sadow, Bert W. O'malley, Olivier Chassande, Karine Gauthier, Jacques Samarut, Jianming Xu, Roy E. WeissAbstract:Isoforms of the Thyroid Hormone receptor (TR)α and TRβ genes mediate Thyroid Hormone action. How TR isoforms modulate tissue-specific Thyroid Hormone (TH) action remains largely unknown. The steroi...
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Resistance to Thyroid Hormone in the Absence of Mutations in the Thyroid Hormone Receptor Genes
Current Opinion in Endocrinology & Diabetes, 2000Co-Authors: Samuel Refetoff, Peter M. Sadow, Joachim Pohlenz, Sirimon Reutrakul, Kimberly Dennis, Deborah Mannavola, Roy E. WeissAbstract:Resistance to Thyroid Hormone (RTH) is a syndrome of reduced tissue sensitivity to Thyroid Hormone. In the majority of subjects, RTH is caused by mutant Thyroid Hormone receptors (TR) s molecules that interfere with the function of the normal TRs, thus resulting in a dominant mode of inheritance. RTH caused by TRβ gene deletion, on the other hand, is inherited as a recessive trait. In as many as 15% of families, RTH manifests in the absence of a TR gene abnormality. The clinical manifestations and laboratory abnormalities in such subjects are not significantly different than those found in individuals with TRs defects. We propose that the molecular defect causing RTH without TR gene mutations must be elsewhere in the pathway of Thyroid Hormone action.
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A Novel Point Mutation of Thyroid Hormone Receptor β Gene in a Family with Resistance to Thyroid Hormone
Thyroid, 1997Co-Authors: Tomohisa Nagashima, Kazumichi Onigata, Hideki Yagi, Kanji Nagashima, Akihiro Sakurai, Yoko Nomura, Akihiro Morikawa, Gail S. Matazow, R.m. Couch, Roy E. WeissAbstract:Resistance to Thyroid Hormone (RTH) is characterized by variable tissue hyporesponsiveness to Thyroid Hormone caused by mutations of Thyroid Hormone receptor β (TRβ) gene. We found a novel point mu...
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Thyrotropin Regulation by Thyroid Hormone in Thyroid Hormone Receptor β-Deficient Mice1
Endocrinology, 1997Co-Authors: Roy E. Weiss, Douglas Forrest, Joachim Pohlenz, Tom Curran, Samuel RefetoffAbstract:Thyroid Hormone responsive genes can be both positively and negatively regulated by Thyroid Hormone. TSH is down-regulated by Thyroid Hormone and rises during Thyroid Hormone deprivation. Because both Thyroid Hormone receptor (TR) α and β genes are expressed in the pituitary gland, it is unclear what the relative roles of TRα and TRβ are in TSH regulation. Experiments using over expression of artificial genes have yielded conflicting results. The TRβ knock-out mouse that lacks both TRβ1 and TRβ2 isoforms provides a model to examine the role of these receptors in TSH regulation. TRβ deficient (TRβ−/−) and wild-type (TRβ+/+) mice of the same strain were deprived of Thyroid Hormone by feeding them a low iodine diet containing propylthiouracil and were then treated with different doses of L-T3 and L-T4. Thyroid Hormone deprivation rapidly increased the serum TSH level in both TRβ+/+ and TRβ−/− mice, reaching a similar level in the absence of Thyroid Hormone. In contrast, the decline of serum TSH by treatment ...
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Effect of Thyroid Hormone on growth: Lessons from the syndrome of resistance to Thyroid Hormone
Endocrinology and Metabolism Clinics of North America, 1996Co-Authors: Roy E. Weiss, Samuel RefetoffAbstract:Thyroid Hormone deprivation results in deleterious effects on bone growth. Delayed bone development is mediated by a direct effect of Thyroid Hormone on bone and an indirect effect of the Hormone on growth Hormone release and IGF-I action. Both Thyroid Hormone receptors alpha and beta are expressed in bone cells. To examine the role of Thyroid Hormone receptor beta on bone, the growth abnormalities in the human syndrome of resistance to Thyroid Hormone caused by mutations in the Thyroid Hormone receptor beta gene are reviewed. These mutant receptors reduce the tissue responsiveness to Thyroid Hormone, producing variable degrees of Thyroid Hormone deprivation in some tissues. With regard to bone, relative Thyroid Hormone deficiency caused by the mutant Thyroid Hormone receptor beta produces short stature and delayed bone growth. These observations indicate that an intact Thyroid Hormone receptor beta is required for normal bone development and growth.
Faith B Davis - One of the best experts on this subject based on the ideXlab platform.
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Promotion by Thyroid Hormone of cytoplasm-to-nucleus shuttling of Thyroid Hormone receptors.
Steroids, 2008Co-Authors: Paul J Davis, Faith B DavisAbstract:Abstract Confocal microscopy and cell fractionation studies have revealed the residence of nuclear Thyroid Hormone receptors (TR) in cytoplasm. Treatment of cells with the Hormone ( l -thyroxine or 3,5,3′-triiodo- l -thyronine, T 3 ) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRβ1 isoform may be found in cytoplasm of Thyroid Hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRα1 is also increased by T 3 . It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid Hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for Thyroid Hormone on integrin αvβ3 that does not share homologies with TR may move to the cell nucleus in Thyroid Hormone-treated cells. Because cells in the intact organism are tonically exposed to Thyroid Hormone, the latter is likely to contribute to the basal rate of nuclear import of Thyroid Hormone receptors.
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Promotion by Thyroid Hormone of cytoplasm-to-nucleus shuttling of Thyroid Hormone receptors.
Steroids, 2008Co-Authors: Paul J Davis, Faith B DavisAbstract:Confocal microscopy and cell fractionation studies have revealed the residence of nuclear Thyroid Hormone receptors (TR) in cytoplasm. Treatment of cells with the Hormone (L-thyroxine or 3,5,3'-triiodo-L-thyronine, T(3)) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRbeta1 isoform may be found in cytoplasm of Thyroid Hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRalpha1 is also increased by T(3). It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid Hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for Thyroid Hormone on integrin alphavbeta3 that does not share homologies with TR may move to the cell nucleus in Thyroid Hormone-treated cells. Because cells in the intact organism are tonically exposed to Thyroid Hormone, the latter is likely to contribute to the basal rate of nuclear import of Thyroid Hormone receptors.
E. Chester Ridgway - One of the best experts on this subject based on the ideXlab platform.
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Thyroid Hormone resistance syndromes.
The American Journal of Medicine, 1993Co-Authors: Michael T. Mcdermott, E. Chester RidgwayAbstract:Abstract The Thyroid Hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of Thyroid Hormone. Generalized resistance to Thyroid Hormone (GRTH) is characterized by resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum Thyroid Hormone levels and inappropriately normal or elevated Thyroid-stimulating Hormone (TSH) but are usually clinically euThyroid and require no treatment. Selective pituitary resistance to Thyroid Hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum Thyroid Hormone levels and normal or elevated TSH levels and are clinically thyrotoxic. Therapy is usually necessary, but current choices are not completely satisfactory. Selective peripheral resistance to Thyroid Hormone (PerRTH) is characterized by resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum Thyroid Hormone and TSH levels but was clinically hypoThyroid and unproved with Thyroid Hormone administration. All of these disorders are probably more common than is generally recognized and are often misdiagnosed and inappropriately treated. GRTH, in most cases studied, results from a mutation in the Thyroid Hormone receptor β gene causing an amino acid substitution in or a partial or complete deletion of the Thyroid Hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined.
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Thyroid Hormone resistance syndromes.
The American journal of medicine, 1993Co-Authors: Michael T. Mcdermott, E. Chester RidgwayAbstract:The Thyroid Hormone resistance syndromes are disorders in which the body's tissues are resistant to the effects of Thyroid Hormone. Generalized resistance to Thyroid Hormone (GRTH) is characterized by resistance in the pituitary gland and in most or all of the peripheral tissues. Affected individuals have elevated serum Thyroid Hormone levels and inappropriately normal or elevated Thyroid-stimulating Hormone (TSH) but are usually clinically euThyroid and require no treatment. Selective pituitary resistance to Thyroid Hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues. Patients have elevated serum Thyroid Hormone levels and normal or elevated TSH levels and are clinically thyrotoxic. Therapy is usually necessary, but current choices are not completely satisfactory. Selective peripheral resistance to Thyroid Hormone (PerRTH) is characterized by resistance in peripheral tissues but not in the pituitary. The only patient thus far described had normal serum Thyroid Hormone and TSH levels but was clinically hypoThyroid and improved with Thyroid Hormone administration. All of these disorders are probably more common than is generally recognized and are often misdiagnosed and inappropriately treated. GRTH, in most cases studied, results from a mutation in the Thyroid Hormone receptor beta gene causing an amino acid substitution in or a partial or complete deletion of the Thyroid Hormone-binding domain of the receptor. The causes of PRTH and PerRTH remain to be determined.