Thyroid hormone receptors in health and disease.
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Thyroid hormones (TH) play a key role in energy homeostasis throughout life. Thyroid hormone production and secretion by the thyroid gland is regulated via the hypothalamus-pituitary-thyroid (HPT)-axis. Thyroid hormone has to be transported into the cell, where it can bind to the thyroid hormone receptor (TR) in the nucleus to exert its effect on cellular gene-transcription. Mutations in both the THRA and THRB gene have been described, each inducing a characteristic phenotype clearly showing the selective effect of an excess or shortage of thyroid hormone in specific TRα and TRβ regulated organs. Profound changes in thyroid hormone metabolism occur during a variety of non-thyroidal illnesses, each associated with reduced TR expression in a tissue-specific manner. However, thyroid hormone action at the tissue level during illness is not a simple reflection of the extent of TR expression as illness has additional differential effects on local thyroid hormone availability in various organs.Keywords:
Thyroid hormone receptor
Endocrine gland
Thyroid disease
Hypothalamic–pituitary–thyroid axis
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We have extensively characterized the sequences of the rat growth hormone (rGH) promoter required for induction by T3 (thyroid hormone, 3,5,3'-L-triiodothyronine) in a transient transfection system. Oligonucleotides containing portions of the rGH promoter sequence with various deletions and point mutations were placed upstream of the first 137 base pairs of the rGH promoter or the heterologous herpes virus thymidine kinase promoter in chloramphenicol acetyltransferase expression vectors. The rGH137 and thymidine kinase promoters show no or minimal response to T3 in the basal state. The constructs were tested in GH4C1 rat pituitary cells and COS cells (functionally deficient in thyroid hormone receptor) with and without a co-transfected plasmid expressing a beta type c-erbA gene coding for a functional T3 receptor. Oligonucleotides containing the T3 receptor binding site confer hormone-dependent induction in a manner that is independent of either orientation or variation in position on the helix relative to the promoter. Point mutations in the sequence -189 to -173 result in loss of T3 induction, and bases between -173 and -167 were also required for a full T3 response. The minimal length to confer T3 induction to the rGH promoter was 23 base pairs (-190 to -167). Point mutations creating a perfect duplication of 7 base pairs within the receptor binding site conferred 12-fold T3 response to the rGH137 promoter, 3-fold greater than the wild type rGH237 construct. T3 inductibility was also transferred to the thymidine kinase promoter by an oligonucleotide containing the sequence -200 to -157, demonstrating that cell type specific elements located 3' to 157 of the rGH promoter are not required for thyroid hormone responsiveness.
Thyroid hormone receptor
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Thyroid hormone receptor
Endocrine gland
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Thyroid dysfunction,including hyperthyroidism and hypothyroidism,is often associated with impaired glucose regulation.Hyperthyroidism was thought to be mainly related with insulin resistance,though recent reports showed that hypothyroidism could decrease insulin sensitivity.Furthermore,thyroid hormone has also been found to regulate the function of islet β cells.An appropriate level of thyroid hormone is a survival factor for islet β cells undergoing apoptosis,while excessive thyroid hormone may cause the dysfunction of islet β cells.Thyroid hormone can influence β cells by different pathways including binding to nuclear receptors,thyrotropin releasing hormone,etc.
Key words:
Thyroid hormone; Islet β cells; Nuclear receptors; Thyrotropin releasing hormone
Thyroid hormone receptor
Endocrine gland
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Thyroid hormone receptor
Endocrine gland
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The pineal gland hormone melatonin regulates diverse endocrine activities such as thyroid hormone regulation during different physiological condition of the organism. Melatonin exerts most of physiological activities thro ugh its membrane bound MT1 and MT2 receptors. The present research was carried out to study the effects of exogenous melatonin on thyroxin e (T 4 ), thyrotropin (TSH) hormone levels and expression patterns of melatonin receptor (MT1 and MT2) proteins on thyroid gland during different age groups (2 months, 4 months and 8 months) of male and female Swiss albino mice. In male mice group, melatonin treatment can cause the inhibition of T 4 hormone via unaltered TSH level during 2 months and 4 months age group, but in 8 months it increased the level of T 4 as well as TSH level. In female mice group, melatonin elevated the level of T 4 through unaltered the level of TSH during all age groups of mice. However melatonin also significantly decreased the MT1 receptor p roteins expression of thyroid gland in both male and female mice. Whereas MT2 receptor proteins of thyroid gland were expressed differentially due to melatonin supplementation during different age groups of male and female mice. The findings of our present study suggested that melatonin age and sex differentially effects on T 4 hormone. The present study also suggested that melatonin might be prefers its MT2 receptors present on thyroid gland for regulation of T 4 hormone secretion which also depends on age a nd sex (male or female) of
Thyroid hormone receptor
Endocrine gland
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Thyroid hormones regulate crucial processes in vertebrates such as reproduction, development and energy metabolism. Endocrine disruption via the thyroid hormone system is gaining more attention both from scientists and regulators, because of the increasing incidence of hormone-related cancers and developmental defects, and the requirement that newly marketed compounds are tested for thyroid hormone disruption. To reduce the number of experimental animals used and to increase the insight into the mechanisms of toxic interference with the thyroid hormone receptor function, we developed and validated functional in vitro bioassays for thyroid hormone receptor-mediated toxicity. These assays enable quick identification and quantification of specific thyroid hormone receptor disrupting potency of compounds and contribute to the further establishment of a battery of in vitro tests for hazard identification of thyroid active compounds.
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Thyroid hormone receptor
Endocrine gland
Thyroid-stimulating hormone
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Thyroid hormones (TH) play a key role in energy homeostasis throughout life. Thyroid hormone production and secretion by the thyroid gland is regulated via the hypothalamus-pituitary-thyroid (HPT)-axis. Thyroid hormone has to be transported into the cell, where it can bind to the thyroid hormone receptor (TR) in the nucleus to exert its effect on cellular gene-transcription. Mutations in both the THRA and THRB gene have been described, each inducing a characteristic phenotype clearly showing the selective effect of an excess or shortage of thyroid hormone in specific TRα and TRβ regulated organs. Profound changes in thyroid hormone metabolism occur during a variety of non-thyroidal illnesses, each associated with reduced TR expression in a tissue-specific manner. However, thyroid hormone action at the tissue level during illness is not a simple reflection of the extent of TR expression as illness has additional differential effects on local thyroid hormone availability in various organs.
Thyroid hormone receptor
Endocrine gland
Thyroid disease
Hypothalamic–pituitary–thyroid axis
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Thyroid hormone receptor
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Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α, β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify the effects of mutant TRβ on pituitary size.High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist).Patients with mutant TRβ (resistance to thyroid hormone β, RTHβ) showed elevated free tri-iodothyronine/thyroxine levels with normal thyroid-stimulating hormone levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35) = 7.05, P = 0.012, partial η2 = 0.17).RTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.
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Endocrine gland
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