Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.
Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.
A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively.
A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.
High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRB gene (also known as NR1A2, THRB1, or ERBA2 gene) as several isoforms produced by alternative splicing. Mutations in the THRB gene cause THYROID HORMONE RESISTANCE SYNDROME.
Tumors or cancer of the THYROID GLAND.
The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.
High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRA gene (also known as NR1A1, THRA1, ERBA or ERBA1 gene) as several isoforms produced by alternative splicing.
Pathological processes involving the THYROID GLAND.
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.
A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.
An inherited autosomal recessive trait, characterized by peripheral resistance to THYROID HORMONES and the resulting elevation in serum levels of THYROXINE and TRIIODOTHYRONINE. This syndrome is caused by mutations of gene THRB encoding the THYROID HORMONE RECEPTORS BETA in target cells. HYPOTHYROIDISM in these patients is partly overcome by the increased thyroid hormone levels.
A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. EC 1.11.1.8.
Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.
Blood tests used to evaluate the functioning of the thyroid gland.
A small circumscribed mass in the THYROID GLAND that can be of neoplastic growth or non-neoplastic abnormality. It lacks a well-defined capsule or glandular architecture. Thyroid nodules are often benign but can be malignant. The growth of nodules can lead to a multinodular goiter (GOITER, NODULAR).
Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.
A metabolite of THYROXINE, formed by the peripheral enzymatic monodeiodination of T4 at the 5 position of the inner ring of the iodothyronine nucleus.
Surgical removal of the thyroid gland. (Dorland, 28th ed)
A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)
Agents that are used to treat hyperthyroidism by reducing the excessive production of thyroid hormones.
A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
Profound physical changes during maturation of living organisms from the immature forms to the adult forms, such as from TADPOLES to frogs; caterpillars to BUTTERFLIES.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.
These metabolites of THYROXINE are formed by the deiodination of T3 or reverse T3.
A group of metabolites derived from THYROXINE and TRIIODOTHYRONINE via the peripheral enzymatic removal of iodines from the thyroxine nucleus. Thyronine is the thyroxine nucleus devoid of its four iodine atoms.
A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme.
Enlargement of the THYROID GLAND that may increase from about 20 grams to hundreds of grams in human adults. Goiter is observed in individuals with normal thyroid function (euthyroidism), thyroid deficiency (HYPOTHYROIDISM), or hormone overproduction (HYPERTHYROIDISM). Goiter may be congenital or acquired, sporadic or endemic (GOITER, ENDEMIC).
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE.
An adenocarcinoma of the thyroid gland, in which the cells are arranged in the form of follicles. (From Dorland, 27th ed)
A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.
A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.
Conditions of abnormal THYROID HORMONES release in patients with apparently normal THYROID GLAND during severe systemic illness, physical TRAUMA, and psychiatric disturbances. It can be caused by the loss of endogenous hypothalamic input or by exogenous drug effects. The most common abnormality results in low T3 THYROID HORMONE with progressive decrease in THYROXINE; (T4) and TSH. Elevated T4 with normal T3 may be seen in diseases in which THYROXINE-BINDING GLOBULIN synthesis and release are increased.
A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy).
Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.
A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
Genes related to the erbA DNA sequence that was first isolated from the avian erythroblastosis virus (ERYTHROBLASTOSIS VIRUS, AVIAN), v-erbA. In cells, erbA genes encode thyroid hormone receptors (RECEPTORS, THYROID HORMONE). Two distinct c-erbA genes have been identified: erbA-alpha located at 17q21; and erbA-beta located at 3p24. Truncations at the N- and C-terminals of erbA result in products resembling v-erbA. Truncations affect hormone responsiveness but not DNA binding capacity.
A condition in infancy or early childhood due to an in-utero deficiency of THYROID HORMONES that can be caused by genetic or environmental factors, such as thyroid dysgenesis or HYPOTHYROIDISM in infants of mothers treated with THIOURACIL during pregnancy. Endemic cretinism is the result of iodine deficiency. Clinical symptoms include severe MENTAL RETARDATION, impaired skeletal development, short stature, and MYXEDEMA.
Inflammatory disease of the THYROID GLAND due to autoimmune responses leading to lymphocytic infiltration of the gland. It is characterized by the presence of circulating thyroid antigen-specific T-CELLS and thyroid AUTOANTIBODIES. The clinical signs can range from HYPOTHYROIDISM to THYROTOXICOSIS depending on the type of autoimmune thyroiditis.
Inorganic binary compounds of iodine or the I- ion.
The beta subunit of thyroid stimulating hormone, thyrotropin. It is a 112-amino acid glycopolypeptide of about 16 kD. Full biological activity of TSH requires the non-covalently bound heterodimers of an alpha and a beta subunit.
An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).
Inflammatory diseases of the THYROID GLAND. Thyroiditis can be classified into acute (THYROIDITIS, SUPPURATIVE), subacute (granulomatous and lymphocytic), chronic fibrous (Riedel's), chronic lymphocytic (HASHIMOTO DISEASE), transient (POSTPARTUM THYROIDITIS), and other AUTOIMMUNE THYROIDITIS subtypes.
Cell surface proteins that bind pituitary THYROTROPIN (also named thyroid stimulating hormone or TSH) and trigger intracellular changes of the target cells. TSH receptors are present in the nervous system and on target cells in the thyroid gland. Autoantibodies to TSH receptors are implicated in thyroid diseases such as GRAVES DISEASE and Hashimoto disease (THYROIDITIS, AUTOIMMUNE).
A 191-amino acid polypeptide hormone secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR), also known as GH or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency.
Transforming proteins encoded by erbA oncogenes from the avian erythroblastosis virus. They are truncated versions of c-erbA, the thyroid hormone receptor (RECEPTORS, THYROID HORMONE) that have retained both the DNA-binding and hormone-binding domains. Mutations in the hormone-binding domains abolish the transcriptional activation function. v-erbA acts as a dominant repressor of c-erbA, inducing transformation by disinhibiting proliferation.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.
Blood proteins that bind to THYROID HORMONES such as THYROXINE and transport them throughout the circulatory system.
A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
An enlarged THYROID GLAND containing multiple nodules (THYROID NODULE), usually resulting from recurrent thyroid HYPERPLASIA and involution over many years to produce the irregular enlargement. Multinodular goiters may be nontoxic or may induce THYROTOXICOSIS.
Therapeutic use of hormones to alleviate the effects of hormone deficiency.
A thiourea antithyroid agent that inhibits the synthesis of thyroid hormone. It is used in the treatment of hyperthyroidism.
A dangerous life-threatening hypermetabolic condition characterized by high FEVER and dysfunction of the cardiovascular, the nervous, and the gastrointestinal systems.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A nuclear co-repressor protein that shows specificity for RETINOIC ACID RECEPTORS and THYROID HORMONE RECEPTORS. The dissociation of this co-repressor from nuclear receptors is generally ligand-dependent, but can also occur by way of its phosphorylation by members of the MAP KINASE SIGNALING SYSTEM. The protein contains two nuclear receptor interaction domains and four repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 1.
The alpha chain of pituitary glycoprotein hormones (THYROTROPIN; FOLLICLE STIMULATING HORMONE; LUTEINIZING HORMONE) and the placental CHORIONIC GONADOTROPIN. Within a species, the alpha subunits of these four hormones are identical; the distinct functional characteristics of these glycoprotein hormones are determined by the unique beta subunits. Both subunits, the non-covalently bound heterodimers, are required for full biologic activity.
Compounds that contain the Cl(=O)(=O)(=O)O- structure. Included under this heading is perchloric acid and the salts and ester forms of perchlorate.
A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.
A thyroid neoplasm of mixed papillary and follicular arrangement. Its biological behavior and prognosis is the same as that of a papillary adenocarcinoma of the thyroid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1271)
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Established cell cultures that have the potential to propagate indefinitely.
Compounds, either natural or synthetic, which block development of the growing insect.
A peptide of 44 amino acids in most species that stimulates the release and synthesis of GROWTH HORMONE. GHRF (or GRF) is synthesized by neurons in the ARCUATE NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, GHRF stimulates GH release by the SOMATOTROPHS in the PITUITARY GLAND.
A family of proteins involved in the transport of monocarboxylic acids such as LACTIC ACID and PYRUVIC ACID across cellular membranes.
Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Structurally, they include polypeptide, protein, and glycoprotein molecules.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
Chronic autoimmune thyroiditis, characterized by the presence of high serum thyroid AUTOANTIBODIES; GOITER; and HYPOTHYROIDISM.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
Surgical removal or destruction of the hypophysis, or pituitary gland. (Dorland, 28th ed)
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
The measurement of an organ in volume, mass, or heaviness.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Elements of limited time intervals, contributing to particular results or situations.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Radiopaque medium used as diagnostic aid.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
A thyroid hormone transport protein found in serum. It binds about 75% of circulating THYROXINE and 70% of circulating TRIIODOTHYRONINE.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
A peptide of about 41 amino acids that stimulates the release of ADRENOCORTICOTROPIC HORMONE. CRH is synthesized by neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the PITUITARY GLAND. CRH can also be synthesized in other tissues, such as PLACENTA; ADRENAL MEDULLA; and TESTIS.
The rate dynamics in chemical or physical systems.
Hormones synthesized from amino acids. They are distinguished from INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS in that their actions are systemic.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.
A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.
Peptide hormones produced by NEURONS of various regions in the HYPOTHALAMUS. They are released into the pituitary portal circulation to stimulate or inhibit PITUITARY GLAND functions. VASOPRESSIN and OXYTOCIN, though produced in the hypothalamus, are not included here for they are transported down the AXONS to the POSTERIOR LOBE OF PITUITARY before being released into the portal circulation.
The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Materials applied to fabrics, bedding, furniture, plastics, etc. to retard their burning; many may leach out and cause allergies or other harm.
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
Autoantibodies that bind to the thyroid-stimulating hormone (TSH) receptor (RECEPTORS, THYROTROPIN) on thyroid epithelial cells. The autoantibodies mimic TSH causing an unregulated production of thyroid hormones characteristic of GRAVES DISEASE.
A benign epithelial tumor with a glandular organization.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Refers to animals in the period of time just after birth.
A glycoprotein that causes regression of MULLERIAN DUCTS. It is produced by SERTOLI CELLS of the TESTES. In the absence of this hormone, the Mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent Mullerian duct, a form of MALE PSEUDOHERMAPHRODITISM.
Using fine needles (finer than 22-gauge) to remove tissue or fluid specimens from the living body for examination in the pathology laboratory and for disease diagnosis.
Hormones produced by the GONADS, including both steroid and peptide hormones. The major steroid hormones include ESTRADIOL and PROGESTERONE from the OVARY, and TESTOSTERONE from the TESTIS. The major peptide hormones include ACTIVINS and INHIBINS.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.
Compounds that contain two halogenated benzene rings linked via an OXYGEN atom. Many polybrominated diphenyl ethers are used as FLAME RETARDANTS.
A product from the iodination of MONOIODOTYROSINE. In the biosynthesis of thyroid hormones, diiodotyrosine residues are coupled with other monoiodotyrosine or diiodotyrosine residues to form T4 or T3 thyroid hormones (THYROXINE and TRIIODOTHYRONINE).
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A compound forming white, odorless deliquescent crystals and used as iodine supplement, expectorant or in its radioactive (I-131) form as an diagnostic aid, particularly for thyroid function tests.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
A collection of NEURONS, tracts of NERVE FIBERS, endocrine tissue, and blood vessels in the HYPOTHALAMUS and the PITUITARY GLAND. This hypothalamo-hypophyseal portal circulation provides the mechanism for hypothalamic neuroendocrine (HYPOTHALAMIC HORMONES) regulation of pituitary function and the release of various PITUITARY HORMONES into the systemic circulation to maintain HOMEOSTASIS.
HORMONES secreted by the gastrointestinal mucosa that affect the timing or the quality of secretion of digestive enzymes, and regulate the motor activity of the digestive system organs.
A condition characterized by a dry, waxy type of swelling (EDEMA) with abnormal deposits of MUCOPOLYSACCHARIDES in the SKIN and other tissues. It is caused by a deficiency of THYROID HORMONES. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips.
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An inorganic compound that is used as a source of iodine in thyrotoxic crisis and in the preparation of thyrotoxic patients for thyroidectomy. (From Dorland, 27th ed)
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and THYROID HORMONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in the transcriptional activation of chromatin regions.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
An immunoglobulin G, often found in the blood of hyperthyroid individuals. It stimulates the thyroid for a longer duration than does thyrotoxin and may cause hyperthyroidism in newborns due to placental transmission.
Anterior pituitary cells that produce THYROID-STIMULATING HORMONE.
Exogenous agents, synthetic and naturally occurring, which are capable of disrupting the functions of the ENDOCRINE SYSTEM including the maintenance of HOMEOSTASIS and the regulation of developmental processes. Endocrine disruptors are compounds that can mimic HORMONES, or enhance or block the binding of hormones to their receptors, or otherwise lead to activating or inhibiting the endocrine signaling pathways and hormone metabolism.
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
An enzyme that catalyzes the conversion of (S)-malate and NAD+ to oxaloacetate and NADH. EC 1.1.1.37.
Proteins prepared by recombinant DNA technology.
A product from the iodination of tyrosine. In the biosynthesis of thyroid hormones (THYROXINE and TRIIODOTHYRONINE), tyrosine is first iodized to monoiodotyrosine.
Spontaneously remitting inflammatory condition of the THYROID GLAND, characterized by FEVER; MUSCLE WEAKNESS; SORE THROAT; severe thyroid PAIN; and an enlarged damaged gland containing GIANT CELLS. The disease frequently follows a viral infection.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Hormones secreted by insects. They influence their growth and development. Also synthetic substances that act like insect hormones.
The largest cartilage of the larynx consisting of two laminae fusing anteriorly at an acute angle in the midline of the neck. The point of fusion forms a subcutaneous projection known as the Adam's apple.
The surgical removal of one or both ovaries.
Stable iodine atoms that have the same atomic number as the element iodine, but differ in atomic weight. I-127 is the only naturally occurring stable iodine isotope.
Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.
April 25th -26th, 1986 nuclear power accident that occurred at Chernobyl in the former USSR (Ukraine) located 80 miles north of Kiev.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Peptides, natural or synthetic, that stimulate the release of PITUITARY HORMONES. They were first isolated from the extracts of the HYPOTHALAMUS; MEDIAN EMINENCE; PITUITARY STALK; and NEUROHYPOPHYSIS. In addition, some hypophysiotropic hormones control pituitary cell differentiation, cell proliferation, and hormone synthesis. Some can act on more than one pituitary hormone.
Hormones produced by invertebrates, usually insects, mollusks, annelids, and helminths.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.
An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity.
Hormones released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). They include a number of peptides which are formed in the NEURONS in the HYPOTHALAMUS, bound to NEUROPHYSINS, and stored in the nerve terminals in the posterior pituitary. Upon stimulation, these peptides are released into the hypophysial portal vessel blood.
An adenocarcinoma containing finger-like processes of vascular connective tissue covered by neoplastic epithelium, projecting into cysts or the cavity of glands or follicles. It occurs most frequently in the ovary and thyroid gland. (Stedman, 25th ed)
Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
Transport proteins that carry specific substances in the blood or across cell membranes.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.
Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
An anti-inflammatory 9-fluoro-glucocorticoid.
Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the ENDOCRINE GLANDS, included are the CHROMAFFIN SYSTEM and the NEUROSECRETORY SYSTEMS.
An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE.
A transcription factor that partners with ligand bound GLUCOCORTICOID RECEPTORS and ESTROGEN RECEPTORS to stimulate GENETIC TRANSCRIPTION. It plays an important role in FERTILITY as well as in METABOLISM of LIPIDS.
Peptides with the ability to stimulate pigmented cells MELANOCYTES in mammals and MELANOPHORES in lower vertebrates. By stimulating the synthesis and distribution of MELANIN in these pigmented cells, they increase coloration of skin and other tissue. MSHs, derived from pro-opiomelanocortin (POMC), are produced by MELANOTROPHS in the INTERMEDIATE LOBE OF PITUITARY; CORTICOTROPHS in the ANTERIOR LOBE OF PITUITARY, and the hypothalamic neurons in the ARCUATE NUCLEUS OF HYPOTHALAMUS.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Hormones produced in the testis.
Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FOLLICLE STIMULATING HORMONE; SOMATOTROPIN; and CORTICOTROPIN). This may result from surgical or radiation ablation, non-secretory PITUITARY NEOPLASMS, metastatic tumors, infarction, PITUITARY APOPLEXY, infiltrative or granulomatous processes, and other conditions.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
The beta subunit of follicle stimulating hormone. It is a 15-kDa glycopolypeptide. Full biological activity of FSH requires the non-covalently bound heterodimers of an alpha and a beta subunit. Mutation of the FSHB gene causes delayed puberty, or infertility.
An anadromous species of SALMON ranging from the Arctic and Pacific Oceans to Monterey Bay, California and inhabiting ocean and coastal streams. It is familiarly known as the coho or silver salmon. It is relatively small but its light-colored flesh is of good flavor.

Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse. (1/1263)

The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue-specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell-Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system.  (+info)

Competition between thyroid hormone receptor-associated protein (TRAP) 220 and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors. Implications for the recruitment of TRAP and p160 coactivator complexes. (2/1263)

Transcriptional activation by nuclear receptors (NRs) involves the concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging complex to the basal transcription machinery. TRAP220, the 220-kDa NR-binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.  (+info)

Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. (3/1263)

The N-CoR/SMRT complex containing mSin3 and histone deacetylase (HDAC) mediates transcriptional repression by nuclear hormone receptors and Mad. The proteins encoded by the ski proto-oncogene family directly bind to N-CoR/SMRT and mSin3A, and forms a complex with HDAC. c-Ski and its related gene product Sno are required for transcriptional repression by Mad and thyroid hormone receptor (TRbeta). The oncogenic form, v-Ski, which lacks the mSin3A-binding domain, acts in a dominant-negative fashion, and abrogates transcriptional repression by Mad and TRbeta. In ski-deficient mouse embryos, the ornithine decarboxylase gene, whose expression is normally repressed by Mad-Max, is expressed ectopically. These results show that Ski is a component of the HDAC complex and that Ski is required for the transcriptional repression mediated by this complex. The involvement of c-Ski in the HDAC complex indicates that the function of the HDAC complex is important for oncogenesis.  (+info)

Proteasome-dependent degradation of the human estrogen receptor. (4/1263)

In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of proteins with short half-lives. The covalent attachment of ubiquitin to lysine residues of targeted proteins is a signal for the recognition and rapid degradation by the proteasome, a large multi-subunit protease. In this report, we demonstrate that the human estrogen receptor (ER) protein is rapidly degraded in mammalian cells in an estradiol-dependent manner. The treatment of mammalian cells with the proteasome inhibitor MG132 inhibits activity of the proteasome and blocks ER degradation, suggesting that ER protein is turned over through the ubiquitin-proteasome pathway. In addition, we show that in vitro ER degradation depends on ubiquitin-activating E1 enzyme (UBA) and ubiquitin-conjugating E2 enzymes (UBCs), and the proteasome inhibitors MG132 and lactacystin block ER protein degradation in vitro. Furthermore, the UBA/UBCs and proteasome inhibitors promote the accumulation of higher molecular weight forms of ER. The UBA and UBCs, which promote ER degradation in vitro, have no significant effect on human progesterone receptor and human thyroid hormone receptor beta proteins.  (+info)

Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. (5/1263)

Coactivators previously implicated in ligand-dependent activation functions by thyroid hormone receptor (TR) include p300 and CREB-binding protein (CBP), the steroid receptor coactivator-1 (SRC-1)-related family of proteins, and the multicomponent TR-associated protein (TRAP) complex. Here we show that two positive cofactors (PC2 and PC4) derived from the upstream stimulatory activity (USA) cofactor fraction act synergistically to mediate thyroid hormone (T3)-dependent activation either by TR or by a TR-TRAP complex in an in vitro system reconstituted with purified factors and DNA templates. Significantly, the TRAP-mediated enhancement of activation by TR does not require the TATA box-binding protein-associated factors of TFIID. Furthermore, neither the pleiotropic coactivators CBP and p300 nor members of the SRC-1 family were detected in either the TR-TRAP complex or the other components of the in vitro assay system. These results show that activation by TR at the level of naked DNA templates is enhanced by cooperative functions of the TRAP coactivators and the general coactivators PC2 and PC4, and they further indicate a potential functional redundancy between TRAPs and TATA box-binding protein-associated factors in TFIID. In conjunction with earlier studies on other nuclear receptor-interacting cofactors, the present study also suggests a multistep pathway, involving distinct sets of cofactors, for activation of hormone responsive genes.  (+info)

Inhibition of nuclear receptor signalling by poly(ADP-ribose) polymerase. (6/1263)

Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclear receptor signalling. PARP bound directly to retinoid X receptors (RXR) and repressed ligand-dependent transcriptional activities mediated by heterodimers of RXR and thyroid hormone receptor (TR). The interacting surface is located in the DNA binding domain of RXRalpha. Gel shift assays demonstrated that PARP bound to TR-RXR heterodimers on the response element. Overexpression of wild-type PARP selectively blocked nuclear receptor function in transient transfection experiments, while enzyme-defective mutant PARP did not show significant inhibition, suggesting that the essential role of poly(ADP-ribosyl) enzymatic activity is in gene regulation by nuclear receptors. Furthermore, PARP fused to the Gal4 DNA binding domain suppressed the transcriptional activity of the promoter harboring the Gal4 binding site. Thus, PARP has transcriptional repressor activity when recruited to the promoter. These results indicates that poly(ADP-ribosyl)ation is a negative cofactor in gene transcription, regulating a member of the nuclear receptor superfamily.  (+info)

Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. (7/1263)

Organochlorine compounds, particularly polychlorinated biphenyls (PCBs), alter serum thyroid hormone levels in humans. Hydroxylated organochlorines have relatively high affinities for the serum transport protein transthyretin, but the ability of these compounds to interact with the human thyroid receptor is unknown. Using a baculovirus expression system in insect cells (Sf9 cells), we produced recombinant human thyroid receptor ss (hTRss). In competitive binding experiments, the recombinant receptor had the expected relative affinity for thyroid hormones and their analogs. In competitive inhibition experiments with PCBs, hydroxylated PCBs (OH-PCBs), DDT and its metabolites, and several organochlorine herbicides, only the OH-PCBs competed for binding. The affinity of hTRss for OH-PCBs was 10,000-fold lower (Ki = 20-50 microM) than its affinity for thyroid hormone (3,3',5-triiodothyronine, T3; Ki = 10 nM). Because their relative affinity for the receptor was low, we tested the ability of OH-PCBs to interact with the serum transport proteins--transthyretin and thyroid-binding globulin (TBG). With the exception of one compound, the OH-PCBs had the same affinity (Ki = 10-80 nM) for transthyretin as thyroid hormone (thyroxine; T4). Only two of the OH-PCBs bound TBG (Ki = 3-7 microM), but with a 100-fold lower affinity than T4. Hydroxylated PCBs have relatively low affinities for the human thyroid receptor in vitro, but they have a thyroid hormonelike affinity for the serum transport protein transthyretin. Based on these results, OH-PCBs in vivo are more likely to compete for binding to serum transport proteins than for binding to the thyroid receptor.  (+info)

Glucose and thyroid hormone co-regulate the expression of the intestinal fructose transporter GLUT5. (8/1263)

Expression of the fructose transporter GLUT5 in Caco-2 cells is controlled by the carbohydrate content of the culture media [Mesonero, Matosin, Cambier, Rodriguez-Yoldi and Brot-Laroche (1995) Biochem. J. 312, 757-762] and by the metabolic status of the cells [Mahraoui, Takeda, Mesonero, Chantret, Dussaulx, Bell, and Brot-Laroche (1994) Biochem. J. 301, 169-175]. In this study we show that, in fully differentiated Caco-2/TC7 cells, thyroid hormone and glucose increase GLUT5 mRNA abundance in a dose-dependent manner. Using Caco-2/TC7 cells stably transformed with various fragments of the GLUT5 promoter inserted upstream of the luciferase reporter gene, we localized the sequences that confer 3,3',5-l-tri-iodothyronine (T3)- and/or glucose-sensitivity to the gene. Glucose responsiveness is conferred by the -272/+41 fragment of the promoter, but it is only with the -338/+41 region that transcription of the luciferase reporter gene is stimulated by T3. This 70 bp fragment from position -338 to -272 of the GLUT5 gene is able to confer T3/glucose-responsiveness to the heterologous thymidine kinase promoter. Electrophoretic-mobility-shift assays demonstrate that thyroid hormone receptors alpha and beta are expressed in Caco-2/TC7 cells. They further show that the -308/-290 region of the GLUT5 promoter binds thyroid hormone receptor/retinoid X receptor heterodimers, and that glucose and/or T3 exert a deleterious effect on the binding of the nuclear protein complex.  (+info)

The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. Among the most important functions of thyroid hormone receptors are regulation of metabolism and heart rate. In addition, they play critical roles in the development of organisms. Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with retinoid X receptor (RXR; which in turn is activated by binding to 9-cis-retinoic acid) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active form of TR. In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator proteins. The DNA/TR/coactivator complex then recruits RNA polymerase that transcribes downstream DNA into messenger ...
Saturable, high-affinity binding sites for 3,5,3-triiodo-L-thyronine (T3) were identified in isolated nuclei and solubilized chromatin extracts of mammary glands, spontaneous mammary tumors, and liver from C3H/HeN mice. Receptor concentration in whole mammary gland nuclei (254 fmol/mg DNA) was only about one-half that of mouse liver nuclei (536 fmol/mg DNA), but in molecular weight (55,000) and in their affinity for various thyroid hormone analogues, the binding was essentially identical. Saturation analysis of T3 binding in a series of individual spontaneous mammary tumors and pooled lactating mammary glands indicated that the concentrations of T3-binding sites of the mammary gland are conserved in the transition to neoplasms and are somewhat increased in the largest tumors. Thyroxine binding was identical in capacity to T3 binding in mammary gland nuclei and nuclear extract but showed a higher binding capacity than did T3 in the largest tumors. High-performance molecular exclusion chromatography did
The availability of synthetic thyroid hormone receptor agonists provides a valuable tool to analyze whether specific receptor isoforms mediate specific physiological responses to thyroid hormone. GC-1 is a thyroid hormone analog displaying selectivity for thyroid hormone receptor ß. We have analyzed the effect of GC-1 on expression of thyroid hormone target genes in the cerebrum and cerebellum. Congenitally hypothyroid rats were treated with single daily doses of either T3 or GC-1. Both compounds similarly induced Purkinje cell protein-2 (PCP-2) in the cerebellum. Expression of RC3 and Rhes in the caudate, and hairless, neurotrophin-3, Reelin, and Rev-ErbA{alpha} in the cerebellum, was analyzed by in situ hybridization on postnatal d 16. Hypothyroidism strongly decreased expression of RC3 and Rhes in the caudate, and hairless, Rev-ErbA{alpha}, and neurotrophin-3 in the cerebellum, and increased Reelin. T3 treatment normalized the expression of all genes. However, GC-1 effectively normalized ...
A paper pointing out the possibility that one particular genetic polymorphism appears to result in the need for a higher dose of levothyroxine than otherwise. SNP rs939348 was on my 23andme analysis...
Thyroid hormone receptors are pokies voyeur gallery nuclear transcription factors that mediate thyroid hormone action on gene expression. Well known are the roles these receptors play in mediating the metabolic and developmental effects of thyroid hormone. TRs, however, can negatively regulate gene promoters as it does in the liganded state with respect to TSH and TRH. In addition, TRs can negatively regulate target gene promoters that carry the AP-1 site, which regulates the expression of genes involved in oncologic transformation and cell proliferation. The role of TRs in tumor progression or growth is unknown.. The authors hypothesized that down regulation of AP-1 by receptors would prevent cell proliferation. It has been well established that there is reduced expression of TRb1 in hepatocellular carcinoma and breast cancer cell lines, which show elevated RAS activation. Uninhibited RAS activation results in tumor formation. Therefore, it would make sense that TRb1 may act as an anti-RAS ...
Thyroid hormone (T3) plays diverse roles in adult organ function and during vertebrate development. The most important stage of mammalian development affected by T3 is the perinatal period when plasma T3 level peaks. Amphibian metamorphosis resembles this mammalian postembryonic period and is absolutely dependent on T3. The ability to easily manipulate this process makes it an ideal model to study the molecular mechanisms governing T3 action during vertebrate development. T3 functions mostly by regulating gene expression through T3 receptors (TRs). Studies in vitro, in cell cultures and reconstituted frog oocyte transcription system have revealed that TRs can both activate and repress gene transcription in a T3-dependent manner and involve chromatin disruption and histone modifications. These changes are accompanied by the recruitment of diverse cofactor complexes. More recently, genetic studies in mouse and frog have provided strong evidence for a role of cofactor complexes in T3 signaling in vivo.
Thyroid hormone (T3) plays diverse roles in adult organ function and during vertebrate development. The most important stage of mammalian development affected by T3 is the perinatal period when plasma T3 level peaks. Amphibian metamorphosis resembles this mammalian postembryonic period and is absolutely dependent on T3. The ability to easily manipulate this process makes it an ideal model to study the molecular mechanisms governing T3 action during vertebrate development. T3 functions mostly by regulating gene expression through T3 receptors (TRs). Studies in vitro, in cell cultures and reconstituted frog oocyte transcription system have revealed that TRs can both activate and repress gene transcription in a T3-dependent manner and involve chromatin disruption and histone modifications. These changes are accompanied by the recruitment of diverse cofactor complexes. More recently, genetic studies in mouse and frog have provided strong evidence for a role of cofactor complexes in T3 signaling in vivo.
THRB - THRB (Myc-DDK-tagged)-Human thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian) (THRB), transcript variant 2 available for purchase from OriGene - Your Gene Company.
The discovery of increasing numbers of genes with overlapping sequences highlights the problem of expression in the context of constraining regulatory elements from more than one gene. This study identifies regulatory sequences encompassed within two genes that overlap in an antisense orientation at their 3 ends. The genes encode the α-thyroid hormone receptor gene (TRα or NR1A1) and Rev-erbα (NR1D1). In mammals TRα pre-mRNAs are alternatively spliced to yield mRNAs encoding functionally antagonistic proteins: TRα1, an authentic thyroid hormone receptor; and TRα2, a non-hormone-binding variant that acts as a repressor. TRα2-specific splicing requires two regulatory elements that overlap with Rev-erbα sequences. Functional mapping of these elements reveals minimal splicing enhancer elements that have evolved within the constraints of the overlapping Rev-erbα sequence. These results provide insight into the evolution of regulatory elements within the context of bidirectional coding sequences.
Thyroid hormone (T3) has been suggested to play a role in herpes simplex virus 1 (HSV-1) replication. It was previously reported that HSV-1 replication was suppressed by T3 in mouse neuroblastoma cells overexpressing thyroid hormone receptor β1 (TRβ1). Using a human neuro-endocrine cells LNCaP differentiated by androgen deprivation, HSV-1 replication was active but decreased by T3 at very low moi, probably due to low copy of TRβ1. In this study, a recombinant HSV-1 was constructed expressing TRβ1 (HSV-1/TRβ1). Infection of Vero cells (very little TRβ1 expression) with HSV-1/TRβ1 exhibited increased replication in the presence of T3 compared to the counterpart without TRβ1 overexpression. Interestingly, HSV-1/TRβ1 infection of differentiated LNCaP cells showed strong suppression of viral replication by T3 and the removal of hormone did not fully reversed the suppression as was observed in parent virus. Quantitative analyses indicated that ICP0 expression was blocked using HSV-1/TRβ1 for ...
DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers. DNA-binding domain of thyroid hormone receptors (TRs) is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which co-ordinates a single zinc atom. TR interacts with the thyroid response element, which is a DNA site with direct repeats of the consensus sequence 5-AGGTCA-3 separated by one to five base pairs, upstream of target genes and modulates the rate of transcriptional initiation. Thyroid hormone receptor (TR) mediates the actions of thyroid hormones, which play critical roles in growth, development, and homeostasis in mammals. They regulate overall metabolic rate, cholesterol and triglyceride levels, and heart rate, and affect mood. TRs are expressed from two separate genes (alpha and beta) in human and each gene generates two isoforms of the receptor through differential promoter usage or splicing. TRalpha functions in the heart to regulate heart rate ...
cytoplasm, cytoskeletal adaptor activity, microtubule binding, thyroid hormone receptor binding, cell cycle arrest, cellular response to starvation, cellular response to thyroid hormone stimulus, microtubule bundle formation, negative regulation of cell growth, negative regulation of erythrocyte differentiation
The protein encoded by this gene is a nuclear receptor that is closely related to the estrogen receptor. Results of both in vitro and in vivo studies suggest that ERRα is required for the activation of mitochondrial genes as well as increased mitochondrial biogenesis.[8][9] This protein acts as a site-specific (consensus TNAAGGTCA) transcription regulator and has been also shown to interact with estrogen and the transcription factor TFIIB by direct protein-protein contact. The binding and regulatory activities of this protein have been demonstrated in the regulation of a variety of genes including lactoferrin, osteopontin, medium-chain acyl coenzyme A dehydrogenase (MCAD) and thyroid hormone receptor genes. It was reported that ERRα can activate reporters containing steroidogenesis factor 1 (SF-1) response elements as a result of transient transfection assays,[10] and a possible role of ERRα in steroidogenesis with relation to SF-1 was subsequently demonstrated in adrenocortical cells.[11] ...
Studies on the autosomal dominant syndrome of thyroid hormone resistance have shown that affected patients have a mutant allele for one of the thyroid hormone receptor (TR) isoforms, TRβ (Refetoff et...
The heart is a major target organ for thyroid hormone (T3) action, and marked changes occur in cardiac faction in patients with hypo- or hyperthyroidism. T3 significantly influences cardiac contractile and electrophysiological function with increasing amounts of T3 enhancing cardiac contractile function and accelerating HR. These effects are mediated by the binding of T3 to specific nuclear TRs. TRs are members of a family of nuclear receptors that includes steroid, retinoic acid, and vitamin D receptors, all closely related to the v-erbA oncogene. TRs are encoded by two different genes: TRα on chromosome 17 and TRβ on chromosome 3. TRα and TRβ isoforms have a similar structure, characterized by an amino-terminal domain, a DNA-binding domain comprises two zinc finger motifs, and a carboxy-terminal ligand-binding domain. The TRα gene generates the TRα1 and TRα2 isoforms that are identical for the first 370 amino acids but differ as a consequence of differential splicing at their C ...
Steroid or nuclear hormone receptors constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. The receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. Nuclear hormone receptors consist of a highly conserved DNA-binding domain that recognises specific sequences, connected via a linker region to a C-terminal ligand-binding domain (IPR000536). In addition, certain nuclear hormone receptors have an N-terminal modulatory domain (IPR001292). The DNA-binding domain can elicit either an activating or repressing effect by binding to specific regions of the DNA known as hormone-response elements [(PUBMED:15242341), (PUBMED:15242339)]. These response elements position the receptors, and the complexes recruited by them, close to the genes of which transcription is affected. The ...
Human follicle stimulating hormone (hFSH) is a gonadotropin involved in the stimulation of ovarian follicles in women and the proper maturation of sperm in men. The receptor, hFSHR, belongs to the G protein-coupled receptor class of hormone receptors and is found embedded in cell membranes. Binding of hFSH to its receptor initiates a complex downstream signaling pathway, the precise intricacies of which are still being determined. Previous research in has suggested that hFSHR is located in lipid rafts, microdomains of the membrane that are made up of a higher concentration of cholesterol, glycosphingolipids, and the protein caveolin.. To better understand the mechanism and effect of hFSHR lipid raft residency, cells from the HEK293 line were treated with a peptide mimetic of transmembrane domain 4 of hFSHR. This peptide includes a sequence consistent with a motif shown in other proteins to interact with caveolin. The putative caveolin interaction motif (phiXphiXXXXphiXXphi) was synthesized along ...
ISBN: OCLC Number: Description: x, pages: illustrations ; 27 cm. Contents: 1. Molecular Mechanisms of Nuclear Thyroid Hormone Action / William W. Chin and .
Principal Investigator:FUNAHASHI Hiroomi, Project Period (FY):1997 - 2000, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:General surgery
Detailed structure-activity relationships of many drugs and hormones indicate that ligand-receptor binding involves the interaction of several functional regions on the ligand with complementary receptor subsites. However most hormone receptor binding models have been based on a simple bimolecular reaction obeying the mass action law. We present a quantitative reinterpretation in pharmacological terms of the theory of flexible polyvalent ligand binding. The model explains: 1) the occurrence of complex binding isotherms showing both apparent heterogeneous and cooperative binding sites; 2) bell-shaped dose response curves; 3) the properties of full and partial agonists; 4) how a given antagonist can be either competitive or noncompetitive depending on concentration used. The classical simple bimolecular interaction between drug and receptor is a limiting case of the model, when steric hindrance completely prevents multiple receptor occupancy, or when the ligand and the receptor interact in ...
Affiliation (based on the past Project Information):Daiichi Shinseikai Hospital,Internal Med.,The Head physician,内科,医長, Research Field:内分泌・代謝学,Endocrinology,Kidney internal medicine,Pathological medical chemistry,Neurology, Keywords:Pax-8,甲状腺ホルモン,NF-κB,PDTC,遺伝子発現,Thyroid hormone,TTF-1,Thyroid hormone receptor,甲状腺ホルモンレセプター,クローニング, # of Research Projects:16, # of Research Products:0
Gene target information for TRIP11 - thyroid hormone receptor interactor 11 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Complete information for TRIP10 gene (Protein Coding), Thyroid Hormone Receptor Interactor 10, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
ASC1 antibody (thyroid hormone receptor interactor 4) for WB. Anti-ASC1 pAb (GTX105780) is tested in Human, Mouse samples. 100% Ab-Assurance.
Gene target information for LOC646939 - similar to thyroid hormone receptor interactor 11 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
A hypophysis feedback g tl s hi ny ban fokozott TSH-termel ssel v laszol, ami fokozott pajzsmirigym k d shez, emelkedett pajzsmirigyhormonszintekhez vezet, a hyperthyreosis jellegzetes t netcsoportja azonban nem alakul ki, mivel a c lszervek rz ketlenek a magas pajzsmirigyhormonszintekre. Az egyes szervek szintj n att l f gg en van hypo- vagy hyperthyreosis, hogy ott a nem m k d TR-beta vagy az p TR-alpha van jelen ...
This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010] ...
Rabbit Polyclonal Anti-TR alpha/NR1A1/Thyroid Hormone Receptor alpha Antibody. Validated: WB. Tested Reactivity: Rat. 100% Guaranteed.
Publisher: University of Delaware. Date Issued: 2014. Abstract: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate many of the actions of the thyroid hormone in growth, development, and differentiation. Over the past decades significant advances have been made in the understanding of TR actions in maintaining normal cellular functions. However, the role/s of TRs in human cancer remain unclear to this day. TR alterations in the form of somatic mutations have been associated with several types of cancer, implying that TRs function as tumor suppressors. These TR mutants are usually impaired in T3-driven gene transcription and in many cases can function as dominant-negative inhibitors of wild-type TR activity. The Koh lab has generated tools to complement mutations with impaired transactivation. The hormone analog QH2 behaves as a functionally orthogonal ligand that rescues the transcriptional activity of the synthetic mutant TRbeta(H435A) that otherwise is not ...
Innate immune cells, including macrophages, have recently been identified as target cells for thyroid hormone. We hypothesized that optimal intracellular concentrations of the active thyroid hormone triiodothyronine (T3) are essential for proinflammatory macrophage function. T3 is generated intracellularly by type 2 deiodinase (D2) and acts via the nuclear thyroid hormone receptor (TR). In zebrafish embryos, D2 knockdown increased mortality during pneumococcal meningitis. Primary murine D2 knockout macrophages exhibited impaired phagocytosis and partially reduced cytokine response to stimulation with bacterial endotoxin. These effects are presumably due to reduced intracellular T3 availability. Knockdown of the main TR in macrophages, TRa, impaired polarization into proinflammatory macrophages and amplified polarization into immunomodulatory macrophages. Intracellular T3 availability and action appear to play a crucial role in macrophage function. Our data suggest that low intracellular T3 ...
CRSP complex subunit 6 (Cofactor required for Sp1 transcriptional activation subunit 6) (Transcriptional coactivator CRSP77) (Vitamin D3 receptor-interacting protein complex 80 kDa component) (DRIP80) (Thyroid hormone receptor-associated protein complex 8 [Source:Uniprot/SWISSPROT;Acc:Q9NVC6]CRSP complex subunit 6 (Cofactor required for Sp1 transcriptional activation subunit 6) (Transcriptional coactivator CRSP77) (Vitamin D3 receptor-interacting protein complex 80 kDa component) (DRIP80) (Thyroid hormone receptor-associated protein complex 8 [Source:Uniprot/SWISSPROT;Acc:Q9NVC6] BY ORTHOLOGY TO: ...
The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in the cardiovascular system through cross-coupling to the phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase Akt pathway. In vascular endothelial cells, the predominant TR isoform is TRalpha1. Treatment of endothelial cells with L-3,5,3-triiodothyronine (T3) increased the association of TRalpha1 with the p85alpha subunit of PI3-kinase, leading to the phosphorylation and activation of Akt and endothelial nitric oxide synthase (eNOS). The activation of Akt and eNOS by T3 was abolished by the PI3-kinase inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor, actinomycin D. To determine the physiological relevance of this PI3-kinase/Akt pathway, we ...
TY - JOUR. T1 - Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor. AU - Kim, Sun Gyun. AU - Lee, Bora. AU - Kim, Dae Hwan. AU - Kim, Juhee. AU - Lee, Seunghee. AU - Lee, Soo Kyung. AU - Lee, Jae W.. PY - 2013. Y1 - 2013. N2 - Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclicAMPresponse ...
TY - JOUR. T1 - Neuron-derived orphan receptor 1 transduces survival signals in neuronal cells in response to hypoxia-induced apoptotic insults. AU - Chio, Chung Ching. AU - Wei, Li. AU - Chen, Tyng Guey. AU - Lin, Chien Min. AU - Shieh, Ja-Ping. AU - Yeh, Poh-Shiow. AU - Chen, Ruei Ming. PY - 2016/6/1. Y1 - 2016/6/1. N2 - Objective Hypoxia can induce cell death or trigger adaptive mechanisms to guarantee cell survival. Neuron-derived orphan receptor 1 (NOR-1) works as an early-response protein in response to a variety of environmental stresses. In this study, the authors evaluated the roles of NOR-1 in hypoxia-induced neuronal insults. methods Neuro-2a cells were exposed to oxygen/glucose deprivation (OGD). Cell viability, cell morphology, caspase-3 activity, DNA fragmentation, and cell apoptosis were assayed to determine the mechanisms of OGD-induced neuronal insults. RNA and protein analyses were carried out to evaluate the effects of OGD on expressions of NOR-1, cAMP response element-binding ...
Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW (Nov 1999). A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. The Journal of Biological Chemistry. 274 (48): 34283-93. doi:10.1074/jbc.274.48.34283. PMID 10567404 ...
The purpose of this work was to judge the carotenoid content and genetic variability of banana accessions through the germplasm collection held at Embrapa Cassava and Tropical Fruits, Brazil. the Embrapa germplasm loan company. 2003a,b,c, 2005; Melo (Wittenberg (1 U/L; Sigma) and 39 L of ultrapure drinking water. The PCR amplification system consisted of a …Read More. ...
Nerve conduction within the mammalian central nervous system is made efficient by oligodendrocyte-derived myelin. Historically, thyroid hormones have a well described role in regulating oligodendrocyte differentiation and myelination during development; however, it remains unclear which thyroid hormone receptors are required to drive these effects. This is a question with clinical relevance since nonspecific thyroid receptor stimulation can produce deleterious side-effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor β action and a potentially limited side-effect profile, promotes in vitro oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells. In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor cells via PDGFαR-CreER;Rosa26-eYFP double-transgenic mice to examine the effect of GC-1 on cellular fate and find that treatment with GC-1 during developmental myelination promotes oligodendrogenesis within the corpus ...
TY - JOUR. T1 - Resistance to thyroid hormone (RTH) syndrome reveals novel determinants regulating interaction of T3 receptor with corepressor. AU - Privalsky, Martin L.. AU - Yoh, Sunnie M.. PY - 2000/1/25. Y1 - 2000/1/25. N2 - Thyroid hormone receptors (T3Rs) both repress and activate gene transcription by interacting with auxiliary factors denoted corepressors and coactivators. Resistance to thyroid hormone (RTH) syndrome in humans is manifested as a failure to respond properly to elevated circulating thyroid hormone. RTH syndrome has been mapped to T3Rβ mutations that alter the transcriptional properties of the receptor, resulting in a dominant negative phenotype. We report here a characterization of a series of RTH mutant T3Rs that exhibit unusual interactions with corepressor. Two mutations in receptor helix 11 (Δ430, Δ432) greatly enhance the ability of the mutant receptors to bind to corepressor. A distinct mutation, V264D, in an omega loop region of the receptor, impairs ...
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Looking for online definition of nuclear hormone receptor in the Medical Dictionary? nuclear hormone receptor explanation free. What is nuclear hormone receptor? Meaning of nuclear hormone receptor medical term. What does nuclear hormone receptor mean?
Thyroid hormones (TH) are critical regulators of several physiological processes, which include development, differentiation and growth in virtually all tissues. In past decades, several studies have shown that changes in TH levels caused by thyroid dysfunction, disruption of deiodinases and/or thyroid hormone receptor (TR) expression in tumor cells, influence cell proliferation, differentiation, survival and invasion in a variety of neoplasms in a cell type-specific manner. The function of THs and TRs in neoplastic cell proliferation involves complex mechanisms that seem to be cell specific, exerting effects via genomic and nongenomic pathways, repressing or stimulating transcription factors, influencing angiogenesis and promoting invasiveness. Taken together, these observations indicate an important role of TH status in the pathogenesis and/or development of human neoplasia. Here, we aim to present an updated and comprehensive picture of the accumulated knowledge and the current understanding ...
Impaired sensitivity to thyroid hormone (previously known as reduced sensitivity to thyroid hormone) describes any process that interferes with the effectiveness of thyroid hormone and includes defects in thyroid hormone action, transport, or metabol
The present invention discloses steroid/thyroid hormone receptor DNA binding domain compositions that determine target gene specificity. The invention further discloses methods converting the target gene specificity of one receptor into the target gene specificity of another. Still further the invention discloses novel assays for identifying ligands for orphan hormone receptors. These assays are especially useful since they avoid the necessity of constructing chimeric genes and proteins in order to search for ligands that can activate a putative receptor.
Symptoms of Generalized resistance to thyroid hormone including 6 medical symptoms and signs of Generalized resistance to thyroid hormone, alternative diagnoses, misdiagnosis, and correct diagnosis for Generalized resistance to thyroid hormone signs or Generalized resistance to thyroid hormone symptoms.
D3 prevents T4 activation and terminates thyroid hormone action by inactivating T3 once both molecules cross the plasma membrane and diffuses in the intracellular compartment toward the cell nucleus (Gereben et al., 2008). The net amount of T3 that ends up in the nucleus and eventually binds to its receptors i.e., TRα and/or TRβ, modifies thyroid hormone signaling by defining a transcriptional footprint that is cell-specific (Wu and Koenig, 2000; Zhang and Lazar, 2000). That hypoxia markedly induces D3 is remarkable, dampening thyroid hormone signaling and slowing down O2 consumption (Simonides et al., 2008). That at the same time trafficking of active D3 is redirected to the nucleus is novel and provides the first evidence that thyroid hormone metabolism occurs in the nuclear compartment, physically closer to where TR-mediated gene transcriptional control takes place (Fig. 8D). It is conceivable that the presence of D3 in the nucleus explains the fast changes in O2 consumption observed in ...
Previous studies by Martínez-González et al7 using NOR1 silencing and our experiments in NOR1-deficient SMCs9 provided evidence that this receptor promotes SMC proliferation in vitro. Although these studies point to an important role for NOR1 in the regulation of SMC proliferation, the contribution of NOR1 to the proliferative response underlying neointima formation and the molecular mechanisms responsible for the mitogenic activity of NOR1 remain unknown. In the present study, we extend these earlier observations and demonstrate that NOR1 deficiency attenuates neointima formation, suggesting an important role of NOR1 signaling for proliferative vascular remodeling.. Consistent with the mitogenic activity of NOR1 in vitro,7,9 our data establish that NOR1 is required for cell cycle progression and cell survival. The main gatekeeper of G1→S phase progression is the Rb tumor suppressor protein,18 and we observed altered Rb phosphorylation in NOR1-deficient SMCs. Conversely, overexpression of ...
The precise mechanisms by which coactivators function to regulate transcription remain unclear. Coactivators have a structural role in serving as focal points for multiple protein-protein interactions including association with many transcriptional activation domains (Verrijzer and Tjian, 1996; Shikama et al., 1997; Xu et al., 1999). These interactions might help recruit components of the basal transcriptional machinery including RNA polymerase to a particular promoter (Barlev et al., 1995; Nakajima et al., 1997a, b). Coactivators can also function as enzymes that modify both other transcriptional regulators and the chromatin environment within which transcription occurs (Brownell and Allis, 1996; Gregory and Horz, 1998). The exact significance of these diverse roles is a topic of substantial research interest.. Among the best studied systems for the analysis of coactivator function is the GCN5p-ADA2p-ADA3p complex (Berger et al., 1992; Candau and Berger, 1996; Candau et al., 1997; Grant et al., ...
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The vitamin D receptor gene encodes the nuclear hormone receptor for vitamin D3 and belongs to the family of trans-acting transcriptional regulatory factors and shows sequence similarity to the steroid and thyroid hormone receptors. Downstream targets of this nuclear hormone receptor are principally involved in mineral metabolism though the receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer. In light of evidence for promoter methylation of the vitamin D receptor in the control of the expression of this gene, we have designed methylation assays that cover many regions of this gene in order to determine its methylation profile in normal individuals, ovarian tumors and ovarian cell lines. We have isolated the DNA from ten tumor tissues and their adjacent normal tissue from four different tumor types; ovarian, breast, colon and cervical. By utilizing a combination of bisulfite sequencing, SNP genotyping, and expression analysis, we show ...
Thrb - Thrb (untagged) - Mouse thyroid hormone receptor beta (Thrb), transcript variant 2, (10ug) available for purchase from OriGene - Your Gene Company.
Abcam provides specific protocols for Anti-Thyroid Hormone Receptor beta antibody [J52] (ab2744) : Recommended IP& WB protocol with ab2743 and ab2744…
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Retinoids exert biologic effects such as potent growth inhibitory and cell differentiation activities and are used in the treatment of hyperproliferative dermatological diseases. These effects are mediated by specific nuclear receptor proteins that are members of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. RARRES1, RARRES2, and RARRES3 are genes whose expression is upregulated by the synthetic retinoid tazarotene. RARRES3 is thought act as a tumor suppressor or growth regulator. [provided by RefSeq, Jul 2008 ...
CC Grand Rounds: (1) More Than Meets the Eye: Developmental Functions of Thyroid Hormone (2) Weight Gain: Can We Blame the Thyroid? The Metabolic Effects of Thyroid Hormone
Anti human TR alpha | mouse monoclonal antibodyPP-H2804-00 100 µl | 675.00 EUR Please ask for special prices for two or more vials ...
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Your physician may recommend a hormone receptor test to help determine treatment options and to help learn more about the tumor. This test can help to predict whether the cancer cells are sensitive to hormones.. The hormone receptor test measures the amount of certain proteins (called hormone receptors) in cancer tissue. Hormones (such as estrogen and progesterone that naturally occur in the body) can attach to these proteins. If the test is positive, it is indicating that the hormone is probably helping the cancer cells to grow. In this case, hormone therapy may be given to block the way the hormone works and help keep the hormone away from the cancer cells (hormone receptors). If the test is negative, the hormone does not affect the growth of the cancer cells, and other effective cancer treatments may be given. Always discuss the results of the hormone receptor test with your physician.. If the test indicates that the hormones are affecting your cancer, the cancer may be treated in one of ...
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Many chemicals used in hydraulic fracturing, or fracking, can disrupt not only the human bodys reproductive hormones but also the glucocorticoid and thyroid hormone receptors, which are necessary to maintain good health, a new study finds. The results were presented … Read the rest. ...
Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor Regulates Enhanced Activation of Signal Transducer and Activator of Transcription 3 by Epstein-Barr Virus-Derived Epstein-Barr Nuclear Antigen 2 (2009 ...
Health,Thyroid hormone plays a major role in the development of a fetus. Acco...Researchers studied extended members of a large family in which both...Thus researchers say their data shows for the first time in humans...,Naturally,Occurring,Hormone,Can,Lead,To,Miscarriage,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Retinoid X nuclear receptors (RXRs) are ligand-dependent transcriptional modulators that execute their biological action through the generation of functional heterodimers. Biochemical data indicate that, in the absence of ligand, RXR can exist as an inactive tetramer and that its dissociation, induced by ligand, is important for receptor activation. When RXRa is freed from the tetramer, it forms heterodimers with obligated partners such as RAR, which are protective in cancer. The RXR-tetramer interface is assembled from amino acids that are conserved across several closely related receptors. A single point mutation on RXRa, S427F, which is found in 5% of patients with bladder cancer, is located exactly at the tetramerization interface; however its mechanism of action is unknown. To understand the effect of S427F mutation on the stability of the RXRa tetramer, we performed MD simulations ...
Dr. Bjorn Vennstrom and colleagues in Spain and at the Karolinska Institute (Sweden) have identified novel neural functions of thyroid hormone (TH), revealing that it is required during discrete periods of brain development to confer
Gotten sick lately? So sick that you have to take antibiotics? It happens to the best of us. But, what happens when you take thyroid hormones
Blog on anti-Melanin Concentrating Hormone Receptor1 antibody product: The Melanin Concentrating Hormone Receptor1 n/a (Catalog #MBS611370) is an Antibody produced from Rabbit ...
Three members have been identified in humans nerve Growth factor IB (Nur77, or NR4A1), nuclear receptor related 1 protein (Nurr1, or NR4A2), and neuron-derived orphan receptor 1 (Nor-1, or NR4A3 ...
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"Thyroid Hormones, Silencing Mediator for Retinoid and Thyroid Receptors and Prognosis in Primary Breast Cancer" Anticancer Res ... Govindaraj V, Yaduvanshi NS, Krishnamachar H, Rao AJ - "Expression of thyroid-stimulating hormone receptor, octamer-binding ... Fröhlich E, Wahl R - "Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases" Front ... Kim EY, Chang Y, Lee KH, Yun JS, Park YL, Park CH, Ahn J, Shin H, Ryu S - "Serum concentration of thyroid hormones in abnormal ...
The Coconut Diet - Thyroid Health A Key to Weight Loss Health / Alternative Medicine ... impairment of the conversion of thyroid hormone T4 to T3 occurs, which is symptomatic of hypothyroidism. To create the enzymes ... No chlorine or fluorides to confuse receptor cells. High protein diet with leafy dark green vegetables to control insulin. Plus ... Re: The Coconut Diet - Thyroid Health A Key to Weight Loss One of the Thyroid problems is related to iodine if you do not have ...
"Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase ... Wie J, Kim J, Ha K, Zhang YH, Jeon JH, So I - " Dexamethasone activates transient receptor potential canonical 4 (TRPC4) ... Thyroid. Maes M, Vandewoude M, Schotte C, Martin M, Blockx P - "Suppressive effects of dexamethasone on hypothalamic-pituitary- ... Mitchell J, Bansal A - "Dexamethasone increases G alpha q-11 expression and hormone-stimulated phospholipase C activity in UMR- ...
11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.. 11/13/13 PET ... Thyroid Eye Disease. 2003. Decompression surgery in 2009; eyelid lowering surgery in 2010.. Diagnosed: June 2010, liver mets. ... 11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.. 11/13/13 PET ... 11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.. 11/13/13 PET ...
11/11/13 Finally get hormone receptor results from lung biopsy of 4/2/13. My cancer is no longer ER positive.. 11/13/13 PET ... Thyroid Eye Disease. 2003. Decompression surgery in 2009; eyelid lowering surgery in 2010.. Diagnosed: June 2010, liver mets. ... Thyroid Eye Disease. 2003. Decompression surgery in 2009; eyelid lowering surgery in 2010.. Diagnosed: June 2010, liver mets. ... Thyroid Eye Disease. 2003. Decompression surgery in 2009; eyelid lowering surgery in 2010.. Diagnosed: June 2010, liver mets. ...
  • Recent studies showed increased serum levels of thyroid-stimulating hormone (TSH), with subclinical or manifest hypothyroidism in 10.0-19.7% of breast cancer patients (3, 4). (poisonfluoride.com)
  • Because the longer chain fatty acids are deposited in cells more often as rancid and oxidizing fat, impairment of the conversion of thyroid hormone T4 to T3 occurs, which is symptomatic of hypothyroidism. (projectavalon.net)
  • Carbone DL, Zuloaga DG, Lacagnina AF, McGivern RF, Handa RJ - "Exposure to dexamethasone during late gestation causes female-specific decreases in core body temperature and prepro-thyrotropin-releasing hormone expression in the paraventricular nucleus of the hypothalamus in rats" Physiol Behav (2012)108:6-12. (poisonfluoride.com)
  • Considerable research has shown that trans fatty acids, present when vegetable oils are highly refined (hydrogenated or partially hydrogenated), are especially damaging to cell tissue and can have a negative affect on the thyroid as well as health in general. (projectavalon.net)
  • Forhead AJ, Jellyman JK, Gardner DS, Giussani DA, Kaptein E, Visser TJ, Fowden AL - "Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus" Endocrinology 148(2):800-5 (2007) doi: 10.1210/en.2006-1194. (poisonfluoride.com)
  • Buimer M, van Wassenaer AG, Kok JH - "Postnatal administration of dexamethasone for weaning off the ventilator affects thyroid function" Neonatology. (poisonfluoride.com)

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