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Thyrotropin Receptor
The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that responds to thyroid-stimulating hormone (also known as "thyrotropin") and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G protein-coupled receptor superfamily of integral membrane proteins and is coupled to the Gs protein. It is primarily found on the surface of the thyroid epithelial cells, but also found on adipose tissue and fibroblasts. The latter explains the reason of the myxedema finding during Graves disease. In addition, it has also been found to be expressed in the anterior pituitary gland, hypothalamus and kidneys. Its presence in the anterior pituitary gland may be involved in mediating the paracrine signaling feedback inhibition of thyrotropin along the hypothalamus-pituitary-thyroid axis. Function Upon binding circulating TSH, a G-protein signal cascade activates adenylyl cyclase and intracellular levels of cAMP rise ...
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Thyroid-stimulating Hormone
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid. Physiology Hormone levels TSH (with a half-life of about an hour) stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has only a slight effect on metabolism. T4 is converted to triiodothyronine (T3), which is the active hormone that stimulates metabolism. About 80% of this conversion is in the liver and other organs, and 20% in the thyroid itself.
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Thyroxine
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 256 Anterior pituitary gland rect 66 332 342 374 Negative feedback rect 308 436 510 475 Thyroid gland rect 256 539 563 635 Thyroid hormones rect 357 827 569 856 Catecholamine rect 399 716 591 750 Metabolism desc bottom-left Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre. The major form of thyroid hormone in the blood is thyroxine (T4), whose half-life of around one week is longer ...
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Triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxine (T4) is activated by thyroid-stimulating hormone (TSH), which is released from the anterior pituitary gland. This pathway is part of a closed-loop feedback process: Elevated concentrations of T3, and T4 in the blood plasma inhibit the production of TSH in the anterior pituitary gland. As concentrations of these hormones decrease, the anterior pituitary gland increases production of TSH, and by these processes, a feedback control system stabilizes the level of thyroid hormones in the bloodstream. T3 is the true hormone. Its effects on target tissues are roughly four times more potent than those of T4. Of the thyroid hormone that is produced, just about 20% is T3, whereas 80% is produced as T4. Roughly 85% of the circulating T3 is later fo ...
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G Protein-coupled Receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and ...
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Integral Membrane Protein
An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a significant fraction of the proteins encoded in an organism's genome. Proteins that cross the membrane are surrounded by annular lipids, which are defined as lipids that are in direct contact with a membrane protein. Such proteins can only be separated from the membranes by using detergents, nonpolar solvents, or sometimes denaturing agents. Structure Three-dimensional structures of ~160 different integral membrane proteins have been determined at atomic resolution by X-ray crystallography or nuclear magnetic resonance spectroscopy. They are challenging subjects for study owing to the difficulties associated with extraction and crystallization. In addition, structures of many water-soluble protein domains of IMPs are available in the Prote ...
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Gs Alpha Subunit
The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family. The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene. Function The general function of Gs is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα ...
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Thyroid Epithelial Cell
Thyroid follicular cells (also called thyroid epithelial cells or thyrocytes) are the major cell type in the thyroid gland, and are responsible for the production and secretion of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). They form the single layer of cuboidal epithelium that makes up the outer structure of the almost spherical thyroid follicle. Structure Location Thyroid follicular cells form a simple cuboidal epithelium and are arranged in spherical thyroid follicles surrounding a fluid filled space known as the colloid. The interior space formed by the follicular cells is known as the follicular lumen. The basolateral membrane of follicular cells contains thyrotropin receptors which bind to thyroid-stimulating hormone (TSH) found circulating in the blood. Calcitonin-producing parafollicular cells are also found along the basement membrane of the thyroid follicle, interspersed between follicular cells; and in spaces between the spherical follicles. Para ...
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Thyroglobulin
Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment of the thyroid follicles, accounting for approximately half of the protein content of the thyroid gland. Human TG (hTG) is a homodimer of subunits each containing 2768 amino acids as synthesized (a short signal peptide of 19 aminoacids may be removed from the N-terminus in the mature protein). Thyroglobulin is in all vertebrates the main precursor to thyroid hormones, which are produced when thyroglobulin's tyrosine residues are combined with iodine and the protein is subsequently cleaved. Each thyroglobulin molecule contains approximately 100–120 tyrosine residues, but only a small number (20) of these are subject to iodination by thyroperoxidase in the follicular colloid. Therefore, each Tg molecule forms approximately 10 thyroid hormo ...
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Thyroid Peroxidase
Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones. In humans, thyroperoxidase is encoded by the ''TPO'' gene. Catalyzed reaction + I− + H+ + H2O2 ⇒ + 2 H2O Iodide is oxidized to iodine radical which immediately reacts with tyrosine. + I− + H+ + H2O2 ⇒ + 2 H2O The second iodine atom is added in similar manner to the reaction intermediate 3-iodotyrosine. Function Inorganic iodine enters the body primarily as iodide, I−. After entering the thyroid follicle (or thyroid follicular cell) via a Na+/I− symporter (NIS) on the basolateral side, iodide is shuttled across the apical membrane into the colloid via pendrin, after which thyroid peroxidase oxidizes iodide t ...
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Graves' Disease
Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems. The exact cause of the disease is unclear; however, it is believed to involve a combination of genetic and environmental factors. A person is more likely to be affected if they have a family member with the disease. If one twin is affected, a 30% chance exists that the other twin will also have the disease. The onset of disease may be ...
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Journal Of Endocrinological Investigation
The ''Journal of Endocrinological Investigation'' is a monthly peer-reviewed medical journal covering endocrinology. It was established in 1978 and is published by Springer Science+Business Media on behalf of the Italian Society of Endocrinology, of which it is the official journal. The editor-in-chief is Luigi Bartalena (University of Insubria). According to the ''Journal Citation Reports'', the journal has a 2017 impact factor The impact factor (IF) or journal impact factor (JIF) of an academic journal is a scientometric index calculated by Clarivate that reflects the yearly mean number of citations of articles published in the last two years in a given journal, as i ... of 3.166. References External links * Springer Science+Business Media academic journals Monthly journals Publications established in 1978 English-language journals Endocrinology journals Academic journals associated with learned and professional societies {{medical-journal-stub ...
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G Protein-coupled Receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and a ...
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