Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00002
S. Boyages
A diet deficient in iodine may cause a wide spectrum of illness, collectively termed iodine deficiency disorders (IDDs), that affects people of all ages, but particularly pregnant women, the developing fetus, and the neonate. One thousand million people worldwide are potentially at risk from IDD. Endemic goiter is the most common of these disorders, and its prevalence rises commensurate with the degree of iodine lack, reaching 100% in communities with severe iodine deficiency. Despite the highly visible nature of this condition, the major public health problem attributable to iodine deficiency is its detrimental effects on the developing fetal and neonatal brain. This is expressed clinically in its extreme manifestation as endemic cretinism, a disorder of profound mental and physical disability. Nonetheless, lesser degrees of iodine deficiency, by its effects on maternal-fetal thyroid homeostasis, may also impair brain development, commonly presenting as a generalized reduction in the intellectual potential of a community. All IDDs are preventable. Nevertheless, although the benefits of iodine supplementation were recognized as early as 1816 and iodine supplementation programs have been implemented in various countries since 1924, IDDs remain a significant world health problem. Although the technology and methods of implementation of iodine supplementation programs are relatively simple, the monitoring and assessment of such programs are more difficult. The application of thyroid ultrasonography as a measure of thyroid size and monitoring of neonatal thyroid-stimulating hormone levels have introduced new epidemiologic methods to assess the burden of iodine deficiency on the community.
{"title":"Progress in understanding the clinical consequences of endemic iodine deficiency","authors":"S. Boyages","doi":"10.1097/00060793-199710000-00002","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00002","url":null,"abstract":"A diet deficient in iodine may cause a wide spectrum of illness, collectively termed iodine deficiency disorders (IDDs), that affects people of all ages, but particularly pregnant women, the developing fetus, and the neonate. One thousand million people worldwide are potentially at risk from IDD. Endemic goiter is the most common of these disorders, and its prevalence rises commensurate with the degree of iodine lack, reaching 100% in communities with severe iodine deficiency. Despite the highly visible nature of this condition, the major public health problem attributable to iodine deficiency is its detrimental effects on the developing fetal and neonatal brain. This is expressed clinically in its extreme manifestation as endemic cretinism, a disorder of profound mental and physical disability. Nonetheless, lesser degrees of iodine deficiency, by its effects on maternal-fetal thyroid homeostasis, may also impair brain development, commonly presenting as a generalized reduction in the intellectual potential of a community. All IDDs are preventable. Nevertheless, although the benefits of iodine supplementation were recognized as early as 1816 and iodine supplementation programs have been implemented in various countries since 1924, IDDs remain a significant world health problem. Although the technology and methods of implementation of iodine supplementation programs are relatively simple, the monitoring and assessment of such programs are more difficult. The application of thyroid ultrasonography as a measure of thyroid size and monitoring of neonatal thyroid-stimulating hormone levels have introduced new epidemiologic methods to assess the burden of iodine deficiency on the community.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"320–327"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00004
Arturo Hernandez, D. S. St. Germain
Deiodination in the thyroid gland and extrathyroidal tissues is the predominant mechanism whereby thyroxine is converted into more active and less active thyroid analogues. The deiodinases that catalyze these reactions are now known to constitute a family of structurally related selenoproteins. This review focuses on progress in our understanding of the physiology, biochemistry, and regulation of these enzymes. Recent developments have provided important information about the structure and expression patterns of the type 2 deiodinase, the mechanisms whereby selenocysteine is incorporated into eukaryotic proteins, the effects of selenium deficiency on thyroid hormone metabolism, the important role of the placenta in controlling fetal thyroid hormone levels, and the role of thyroid hormones, growth factors, and cytokines in regulating deiodinase expression in different tissues. With the availability of immunologic and molecular reagents for studying these enzymes, it is expected that our understanding of their structure, function, and physiologic roles will continue to progress at a rapid pace.
{"title":"Selenodeiodinases and their role in thyroid hormone activation and inactivation","authors":"Arturo Hernandez, D. S. St. Germain","doi":"10.1097/00060793-199710000-00004","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00004","url":null,"abstract":"Deiodination in the thyroid gland and extrathyroidal tissues is the predominant mechanism whereby thyroxine is converted into more active and less active thyroid analogues. The deiodinases that catalyze these reactions are now known to constitute a family of structurally related selenoproteins. This review focuses on progress in our understanding of the physiology, biochemistry, and regulation of these enzymes. Recent developments have provided important information about the structure and expression patterns of the type 2 deiodinase, the mechanisms whereby selenocysteine is incorporated into eukaryotic proteins, the effects of selenium deficiency on thyroid hormone metabolism, the important role of the placenta in controlling fetal thyroid hormone levels, and the role of thyroid hormones, growth factors, and cytokines in regulating deiodinase expression in different tissues. With the availability of immunologic and molecular reagents for studying these enzymes, it is expected that our understanding of their structure, function, and physiologic roles will continue to progress at a rapid pace.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"333–340"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00003
J. de Vijlder, H. Bikker, C. Ris-Stalpers, T. Vulsma
Recent advances have been made in the research on structure and function of thyroid peroxidase in the field of the reaction mechanism with respect to the involvement of compound l in iodination and thyroid hormonogenesis. New information has become available concerning the mechanism of thyroid peroxidase autoantibody formation and immunodominant domains on the thyroid peroxidase molecule. In certain types of hereditary congenital hypothyroidism, called total iodide organification defects, thyroid peroxidase is impaired owing to mutations in the thyroid peroxidase gene. Detailed investigations on the proteins expressed in vitro have been described.
{"title":"Structure, function, and relevance of thyroid peroxidase in inherited diseases of the thyroid","authors":"J. de Vijlder, H. Bikker, C. Ris-Stalpers, T. Vulsma","doi":"10.1097/00060793-199710000-00003","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00003","url":null,"abstract":"Recent advances have been made in the research on structure and function of thyroid peroxidase in the field of the reaction mechanism with respect to the involvement of compound l in iodination and thyroid hormonogenesis. New information has become available concerning the mechanism of thyroid peroxidase autoantibody formation and immunodominant domains on the thyroid peroxidase molecule. In certain types of hereditary congenital hypothyroidism, called total iodide organification defects, thyroid peroxidase is impaired owing to mutations in the thyroid peroxidase gene. Detailed investigations on the proteins expressed in vitro have been described.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"328–332"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00009
V. Chatterjee
Resistance to thyroid hormone (RTH) is usually dominantly inherited and associated with diverse mutations in the thyroid hormone receptor (TR) β gene, localizing to three regions (residues 234 to 282, 310 to 353, 429 to 461) in the receptor hormone-binding domain. The mutant receptors are transcrip-tionally impaired owing to reduced ligand binding or coactiva-tor recruitment and also inhibit wild-type receptor action in a dominant negative manner. This dominant negative action of mutant receptors is abrogated by disruption of their binding to DNA, retinoid X receptor, or corepressor, which correlates with the absence of natural mutations in receptor domains mediating these functions. More recently recognized features of RTH include attention-deficit hyperactivity disorder, low body mass index in childhood, and hearing abnormalities. Although both generalized and pituitary RTH are associated with TRβ defects, there is growing evidence that some mutations predispose to the pituitary RTH phenotype, possibly because of their selective dominant negative action in a TRβ2 but not TRβ1 context. Targeted disruption of the mouse TRβ gene recapitulates many features of recessively inherited RTH, but heterozygous mice are normal, confirming that haploinsufficiency at this locus does not result in RTH. The phenotype in TRα mutant mice is quite dissimilar to RTH, suggesting that homologous mutations in TRα1 are unlikely to mediate the human disorder.
{"title":"Molecular genetics and pathophysiology of thyroid hormone resistance","authors":"V. Chatterjee","doi":"10.1097/00060793-199710000-00009","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00009","url":null,"abstract":"Resistance to thyroid hormone (RTH) is usually dominantly inherited and associated with diverse mutations in the thyroid hormone receptor (TR) β gene, localizing to three regions (residues 234 to 282, 310 to 353, 429 to 461) in the receptor hormone-binding domain. The mutant receptors are transcrip-tionally impaired owing to reduced ligand binding or coactiva-tor recruitment and also inhibit wild-type receptor action in a dominant negative manner. This dominant negative action of mutant receptors is abrogated by disruption of their binding to DNA, retinoid X receptor, or corepressor, which correlates with the absence of natural mutations in receptor domains mediating these functions. More recently recognized features of RTH include attention-deficit hyperactivity disorder, low body mass index in childhood, and hearing abnormalities. Although both generalized and pituitary RTH are associated with TRβ defects, there is growing evidence that some mutations predispose to the pituitary RTH phenotype, possibly because of their selective dominant negative action in a TRβ2 but not TRβ1 context. Targeted disruption of the mouse TRβ gene recapitulates many features of recessively inherited RTH, but heterozygous mice are normal, confirming that haploinsufficiency at this locus does not result in RTH. The phenotype in TRα mutant mice is quite dissimilar to RTH, suggesting that homologous mutations in TRα1 are unlikely to mediate the human disorder.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"371"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00008
O. Levy, N. Carrasco
The thyroid iodide (I−) transporter, a Na+/I− symporter (NIS), is an intrinsic 618-amino-acid membrane glycoprotein that catalyzes the accumulation of I− into thyrocytes, an essential step in the biosynthesis of thyroid hormones. Remarkable progress has recently been achieved in the study of NIS at the molecular level as a result of the isolation of the cDNA encoding rat NIS. Among the main accomplishments are the isolation of the cDNA clone encoding human NIS, electrophysiological analysis and elucidation of the mechanism, stoichiometry, and specificity of rat NIS, generation of anti-rat NIS antibodies for use in NIS characterization, proposal and experimental testing of NIS secondary structure models, analysis of the regulation of NIS expression by thyroid-stimulating hormone and I−, characterization of the regulation of the rat NIS gene, elucidation of the genomic organization of human NIS, identification of an NIS mutation in a case of congenital lack of I“ transport, and detection of anti-NIS autoantibodies in thyroid autoimmune disease.
{"title":"Structure and function of the thyroid iodide transporter and its implications for thyroid disease","authors":"O. Levy, N. Carrasco","doi":"10.1097/00060793-199710000-00008","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00008","url":null,"abstract":"The thyroid iodide (I−) transporter, a Na+/I− symporter (NIS), is an intrinsic 618-amino-acid membrane glycoprotein that catalyzes the accumulation of I− into thyrocytes, an essential step in the biosynthesis of thyroid hormones. Remarkable progress has recently been achieved in the study of NIS at the molecular level as a result of the isolation of the cDNA encoding rat NIS. Among the main accomplishments are the isolation of the cDNA clone encoding human NIS, electrophysiological analysis and elucidation of the mechanism, stoichiometry, and specificity of rat NIS, generation of anti-rat NIS antibodies for use in NIS characterization, proposal and experimental testing of NIS secondary structure models, analysis of the regulation of NIS expression by thyroid-stimulating hormone and I−, characterization of the regulation of the rat NIS gene, elucidation of the genomic organization of human NIS, identification of an NIS mutation in a case of congenital lack of I“ transport, and detection of anti-NIS autoantibodies in thyroid autoimmune disease.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"364–370"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00006
Y. Kong
The study of animal models of autoimmune thyroid disease has just entered an exciting era, with major thrusts into new avenues of research. First, the HLA-DRB1 polymorphism has been shown to be a determinant of mouse thyroglobulin (mTg)-induced experimental autoimmune thyroiditis (EAT). Similar to murine class II transgene in conferring EAT susceptibility on resistant mice, the HLA-DRB1*0301 (DR3) transgene permits the induction of EAT with either mTg or human thyroglobulin (hTg). Second, Tg as a potential initiator of autoimmunity is reintroduced by the hTg induction of EAT in mice with a DR3-selected T-cell receptor (TCR) repertoire and by the appearance of anti-Tg in three spontaneous autoimmune thyroiditis models. Third, the completed mTg sequence will enable in-depth study of conserved and unique epitopes on mTg and hTg. Fourth, the importance of appropriate class II genes over other genetic and environmental factors is reemphasized by the secondary role of iodine residues in Tg immunogenicity and the flexibility of the TCR repertoire. Individual DR or DQ transgenes can now be tested without the complication of linkage disequilibrium. Finally, the induction of Graves' disease-like syndrome by immunizing mice with human thyroid-stimulating hormone receptor-transfected cells offers the possibility of establishing a Graves' disease model.
{"title":"Recent developments in the relevance of animal models to Hashimoto's thyroiditis and Graves' disease","authors":"Y. Kong","doi":"10.1097/00060793-199710000-00006","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00006","url":null,"abstract":"The study of animal models of autoimmune thyroid disease has just entered an exciting era, with major thrusts into new avenues of research. First, the HLA-DRB1 polymorphism has been shown to be a determinant of mouse thyroglobulin (mTg)-induced experimental autoimmune thyroiditis (EAT). Similar to murine class II transgene in conferring EAT susceptibility on resistant mice, the HLA-DRB1*0301 (DR3) transgene permits the induction of EAT with either mTg or human thyroglobulin (hTg). Second, Tg as a potential initiator of autoimmunity is reintroduced by the hTg induction of EAT in mice with a DR3-selected T-cell receptor (TCR) repertoire and by the appearance of anti-Tg in three spontaneous autoimmune thyroiditis models. Third, the completed mTg sequence will enable in-depth study of conserved and unique epitopes on mTg and hTg. Fourth, the importance of appropriate class II genes over other genetic and environmental factors is reemphasized by the secondary role of iodine residues in Tg immunogenicity and the flexibility of the TCR repertoire. Individual DR or DQ transgenes can now be tested without the complication of linkage disequilibrium. Finally, the induction of Graves' disease-like syndrome by immunizing mice with human thyroid-stimulating hormone receptor-transfected cells offers the possibility of establishing a Graves' disease model.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"347–353"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1997-10-01DOI: 10.1097/00060793-199710000-00007
M. Szkudlinski, M. Grossmann, B. Weintraub
This paper summarizes current advances in the structure-function relationships of human thyroid-stimulating hormone (TSH) in the context of studies on structurally related gonadotropins. Investigators have now identified specific domains in both protein and carbohydrate components of human TSH that play distinct roles in the synthesis, bioactivity, and metabolic clearance of human TSH. The principles revealed in such studies are essential to understand mechanisms of receptor activation and permit design of novel analogues with potential clinical applications. In particular, superagonists of human TSH and human chorionic gonadotropin have been recently developed using a rational approach combining evolutionary considerations, sequence comparisons, and homology modeling. Such analogues with major increases in receptor-binding affinity and signal transduction are unique tools for studies of both thyroidal and extrathyroidal actions of TSH. Moreover, similar strategies may be used to design analogues of other members of the cystine knot growth factor superfamily.
{"title":"Progress in understanding structure‐function relationships of human thyroid‐stimulating hormone","authors":"M. Szkudlinski, M. Grossmann, B. Weintraub","doi":"10.1097/00060793-199710000-00007","DOIUrl":"https://doi.org/10.1097/00060793-199710000-00007","url":null,"abstract":"This paper summarizes current advances in the structure-function relationships of human thyroid-stimulating hormone (TSH) in the context of studies on structurally related gonadotropins. Investigators have now identified specific domains in both protein and carbohydrate components of human TSH that play distinct roles in the synthesis, bioactivity, and metabolic clearance of human TSH. The principles revealed in such studies are essential to understand mechanisms of receptor activation and permit design of novel analogues with potential clinical applications. In particular, superagonists of human TSH and human chorionic gonadotropin have been recently developed using a rational approach combining evolutionary considerations, sequence comparisons, and homology modeling. Such analogues with major increases in receptor-binding affinity and signal transduction are unique tools for studies of both thyroidal and extrathyroidal actions of TSH. Moreover, similar strategies may be used to design analogues of other members of the cystine knot growth factor superfamily.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"4 1","pages":"354–363"},"PeriodicalIF":0.0,"publicationDate":"1997-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199710000-00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1996-10-01DOI: 10.1097/00060793-199610000-00002
T. Cole
Gene knockouts in mice have been reported for the glucocorti-coid, estrogen, and progesterone receptors, and a natural gene knockout, the testicular-feminized mouse, exists for the androgen receptor. Of these knockouts only the glucocorticoid receptor knockout has profound effects on embryonic development, with defects in the lung and adrenal gland causing perinatal lethality. Female mice with either the estrogen or progesterone receptor knocked out are infertile, as are male mice lacking the estrogen receptor, which have smaller testes and lower sperm production. Estrogen receptor knockout mice also suffer osteoporosis. Progesterone receptor knockout mice fail to display ovarian follicular rupture and normal sexual behavior. Steroid receptor knockout mice thus provide a useful animal model for further studies on steroid action. Recent results with Cre- and FLP-recombinase promise a new generation of gene-targeted mice by production of tissue-specific and ligand-inducible gene knockouts.
{"title":"Steroid receptor knockouts","authors":"T. Cole","doi":"10.1097/00060793-199610000-00002","DOIUrl":"https://doi.org/10.1097/00060793-199610000-00002","url":null,"abstract":"Gene knockouts in mice have been reported for the glucocorti-coid, estrogen, and progesterone receptors, and a natural gene knockout, the testicular-feminized mouse, exists for the androgen receptor. Of these knockouts only the glucocorticoid receptor knockout has profound effects on embryonic development, with defects in the lung and adrenal gland causing perinatal lethality. Female mice with either the estrogen or progesterone receptor knocked out are infertile, as are male mice lacking the estrogen receptor, which have smaller testes and lower sperm production. Estrogen receptor knockout mice also suffer osteoporosis. Progesterone receptor knockout mice fail to display ovarian follicular rupture and normal sexual behavior. Steroid receptor knockout mice thus provide a useful animal model for further studies on steroid action. Recent results with Cre- and FLP-recombinase promise a new generation of gene-targeted mice by production of tissue-specific and ligand-inducible gene knockouts.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"3 1","pages":"363–368"},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199610000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1996-10-01DOI: 10.1097/00060793-199610000-00012
D. Russo, F. Arturi, S. Filetti
Since thyroid-stimulating hormone receptor (TSHR) gene mutations were first detected in autonomously hyperfunctioning thyroid adenomas, considerable progress has been made in defining the role of genetic alterations of the TSHR in thyroid diseases regarding the receptor domains and the amino acid residues involved in mutations responsible for the altered (gain or loss) receptor function; the structure-function relationship based on the in vitro assessment of the different signal transduction pathways activated by the TSHR; the involvement of TSHR alterations in the development of thyroid malignancies; and the functional role and the frequency of TSHR mutations occurring in thyroid disorders. This review summarizes recent findings conceming the localization and the functional role of the naturally occurring TSHR gene mutations in thyroid diseases.
{"title":"Thyroid‐stimulating hormone receptor gene mutations and polymorphisms in thyroid disease","authors":"D. Russo, F. Arturi, S. Filetti","doi":"10.1097/00060793-199610000-00012","DOIUrl":"https://doi.org/10.1097/00060793-199610000-00012","url":null,"abstract":"Since thyroid-stimulating hormone receptor (TSHR) gene mutations were first detected in autonomously hyperfunctioning thyroid adenomas, considerable progress has been made in defining the role of genetic alterations of the TSHR in thyroid diseases regarding the receptor domains and the amino acid residues involved in mutations responsible for the altered (gain or loss) receptor function; the structure-function relationship based on the in vitro assessment of the different signal transduction pathways activated by the TSHR; the involvement of TSHR alterations in the development of thyroid malignancies; and the functional role and the frequency of TSHR mutations occurring in thyroid disorders. This review summarizes recent findings conceming the localization and the functional role of the naturally occurring TSHR gene mutations in thyroid diseases.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"3 1","pages":"428–432"},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199610000-00012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1996-10-01DOI: 10.1097/00060793-199610000-00009
Andreas J. Horlein, T. Heinzel, M. Rosenfeld
During the first decade since the thyroid hormone receptors were cloned as homologues of v-erbA, many promoters regulated by these receptors were identified, and the importance of ligand-dependent and ligand-independent differential control of gene expression was established. In this review, we discuss some reports that mark the inception of the second decade of thyroid hormone receptor research as one in which a clear understanding of the molecular mechanisms of receptor action is likely to be achieved. Solving the crystal structure of the liganded thyroid hormone receptor has provided a conceptual basis for understanding the protein interactions that modulate the gene activation program of nuclear receptors. Many potential cofactors of the thyroid hormone receptor have now been characterized and cloned, providing the next level of definition of the complex regulation of positive and negative control of gene expression. Furthermore, evidence has been obtained for direct interactions between the proteins of the basic poly-merase II transcription machinery with the thyroid hormone receptor that could be responsible for the ligand-independent repression in in vitro systems.
{"title":"Gene regulation by thyroid hormone receptors","authors":"Andreas J. Horlein, T. Heinzel, M. Rosenfeld","doi":"10.1097/00060793-199610000-00009","DOIUrl":"https://doi.org/10.1097/00060793-199610000-00009","url":null,"abstract":"During the first decade since the thyroid hormone receptors were cloned as homologues of v-erbA, many promoters regulated by these receptors were identified, and the importance of ligand-dependent and ligand-independent differential control of gene expression was established. In this review, we discuss some reports that mark the inception of the second decade of thyroid hormone receptor research as one in which a clear understanding of the molecular mechanisms of receptor action is likely to be achieved. Solving the crystal structure of the liganded thyroid hormone receptor has provided a conceptual basis for understanding the protein interactions that modulate the gene activation program of nuclear receptors. Many potential cofactors of the thyroid hormone receptor have now been characterized and cloned, providing the next level of definition of the complex regulation of positive and negative control of gene expression. Furthermore, evidence has been obtained for direct interactions between the proteins of the basic poly-merase II transcription machinery with the thyroid hormone receptor that could be responsible for the ligand-independent repression in in vitro systems.","PeriodicalId":88857,"journal":{"name":"Current opinion in endocrinology & diabetes","volume":"3 1","pages":"412–416"},"PeriodicalIF":0.0,"publicationDate":"1996-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00060793-199610000-00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61609769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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