Thyroid hormone are two hormones produced and excreted by the thyroid gland, namely triiodothyronine ( T 3 ) and thyroxine ( T 4 ). They are a tyrosine-based hormone that is primarily responsible for the regulation of metabolism. T 3 and T 4 are composed partly of iodine. Iodine deficiency leads to a decrease in the production of T 3 and T 4 , enlarges the thyroid tissue and will lead to a disease known as simple goitre. The main form of thyroid hormone in the blood is thyroxine (T 4 ), which has a longer half-life than T 3 . In humans, the ratio of T 4 to T 3 is released into the blood is sometimes claimed to be quite high, but the data of the thyroid removal patient indicates it varies from 4: 1 to 2: 1, the average being 100: 36 (about 2.8: 1). T 4 is converted to T 3 active (three to four times stronger than T 4 ) inside the cell by deiodinases (5'-iodinase). This is further processed by decarboxylation and deiodination to produce iodothyronamine ( T 1 a ) and thyronamine ( T 0 a ). The third isoform deiodinase is an enzyme containing selenium, so the selenium diet is essential for the production of T 3 . Edward Calvin Kendall was responsible for the isolation of thyroxine in 1915.
Video Thyroid hormones
Function
Thyroid hormones work in almost every cell in the body. They act to increase basal metabolic rates, affect protein synthesis, help regulate long bone growth (synergize with growth hormone) and neuronal maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) in a permissive manner. Thyroid hormones are important for proper development and differentiation of all cells of the human body. These hormones also regulate the metabolism of proteins, fats, and carbohydrates, affecting how human cells use energetic compounds. They also stimulate vitamin metabolism. Many physiological and pathological stimuli affect the synthesis of thyroid hormones.
Thyroid hormones cause heat generation in humans. However, thyronamines function through several unknown mechanisms to inhibit neuronal activity; This plays an important role in the hibernation cycle of mammals and moulting behavior of birds. One effect of giving thyronamines is a severe decrease in body temperature.
Maps Thyroid hormones
Medical use
Both T 3 and T 4 are used to treat thyroid hormone deficiency (hypothyroidism). Both are well absorbed by the intestine, so it can be given orally. Levothyroxine is the pharmaceutical name of the produced version of T 4 , which is metabolized more slowly than T 3 and therefore usually requires only once-daily administration. The natural dry thyroid hormone is derived from the python gland, and is a "natural" hypothyroid treatment containing 20% sub> 1 and calcitonin. There is also a synthetic combination of T 3 /T 4 in different ratios (such as liotrix) and pure-T drugs 3 (INN: liothyronine). Levothyroxine Sodium is usually the first treatment tried. Some patients feel they are better at dried thyroid hormones; However, this is based on anecdotal evidence and clinical trials have not demonstrated any benefit to the form of biosynthesis. Thyroid tablets are reported to have different effects, which can be attributed to torsional angle differences around where the reactive molecules are.
Thyronamines have no medical use, although its use has been proposed for controlled hypothermia induction, which causes the brain to enter the protective cycle, useful in preventing damage during ischemic shock.
Synthetic thyroxine was first produced by Charles Robert Harington and George Barger in 1926.
Formulation
Currently most patients are treated with levothyroxine, or similar synthetic thyroid hormones. Different polymorphs of the compounds have different solubility and potency. In addition, natural thyroid hormone supplements from the animal's dry thyroid are still available. Levothyroxine contains only T4 and is therefore largely ineffective for patients who can not convert T4 to T3. These patients may choose to take natural thyroid hormones, because they contain a mixture of T4 and T3, or alternative supplements with synthetic T3 treatments. In this case, synthetic liothyronine is preferred because of the potential difference between natural thyroid products. Several studies have shown that mixed therapy is beneficial for all patients, but the addition of lyothyronine contains additional side effects and the drug should be evaluated individually. Some brands of natural thyroid hormone are FDA approved, but some do not. Thyroid hormones are generally well tolerated. Thyroid hormones are usually harmless to pregnant women or nursing mothers, but should be administered under the supervision of a physician. In fact, if a hypothyroid woman is not treated, her baby is at a higher risk for birth defects. During pregnancy, a woman with a low functioning thyroid also needs to increase her thyroid hormone dose. One exception is that thyroid hormones can exacerbate heart conditions, especially in older patients; Therefore, doctors can start this patient with a lower dose and work to a greater extent to avoid the risk of heart attack.
Production
Middle
Thyroid hormones (T 4 and T 3 ) are produced by the cells of thyroid gland follicles and regulated by TSH created by the anterior pituitary thyrotropes. The effects of T 4 in vivo are mediated via T 3 (T 4 converted to T 3 in the target network). T 3 3- to 5 times more active than T 4 .
Thyroxine (3,5,3 ', 5'-tetraiodothyronine) is produced by the cells of thyroid gland follicles. It is produced as a precursor of thyroglobulin (this is not similar to thyroxine-binding globulin (TBG)), which is broken down by the enzyme to produce an active T 4 .
The steps in this process are as follows:
Thyroglobulin (Tg) is 660 kDa, a dimeric protein produced by thyroid follicle cells and used entirely in the thyroid gland. Thyroxine is produced by attaching the iodine atom to the structure of the protein tyrosine residue ring; thyroxine (T 4 ) contains four iodine atoms, while triiodothyronine (T 3 ), or identical to T 4 , has one less iodine atom per molecule. Protein thyroglobulin accounts for about half of the protein content of the thyroid gland. Each thyroglobulin molecule contains about 100-120 tyrosine residues, a small amount that (& lt; 20) is subjected to iodine catalyzed by thyroperoxidase. The same enzyme then catalyzes the "coupling" of one tyrosine modified with another, via free radical reactions, and when these iodinated biplicate molecules are released by protein hydrolysis, T3 and T4 are the results. Therefore, each molecule of thyroglobulin protein eventually produces a very small amount of thyroid hormone (observed experimentally in the order of 5-6 molecules either T4 or T3 per thyroglobulin original molecule).
More specifically, monoatomic forms, anionic iodide, iodide, - , is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium is transported with iodide from the basolateral side of the membrane into the cell, and then concentrated in the thyroid follicle to about thirty times the concentration in the blood. Then, in the first reaction catalyzed by the thyroperoxidase enzyme, the tyrosine residue in the iodized thyroglobulin protein in their phenol ring, in one or both ortho positions to the phenolic hydroxyl group, yields monoiodotyrosine (MIT) and diiodotyrosine (DIT) each. It introduces 1-2 atoms of iodine element, bound covalently, per tyrosine residue. Further integration of two fully iodinated tyrosine residues, also catalyzed by thyroperoxidase, produces a peptide (still peptide-bound) precursor of thyroxine, and the coupling of one MIT molecule and one DIT molecule produces a precursor comparable to triiodothyronine:
- peptidic MIT peptidic DIT -> peptidic triiodothyronine (finally released as triiodothyronine, T 3 )
- 2 DIT peptidik -> thyroxine peptidik (finally released as thyroxine, T 4 )
(Coupling from DIT to MIT in the opposite sequence produces a substance, rT 3 , which is biologically inactive.) Hydrolysis (the cleavage for individual amino acids) of protein modified by protease and then releases T3 and T4 , as well as non-coupled tyrosine derivatives of MIT and DIT. Hormones T 4 and T 3 are biologically active agents that are central to metabolic regulation.
Peripherals
Thyroxine is believed to be the prohormone and reservoir for the most active and major thyroid hormone T 3 . T 4 is changed as needed in the tissues by iodothyronine deiodinase. Lack of deiodinase may mimic hypothyroidism due to iodine deficiency. T 3 is more active than T 4 , although it is present in an amount less than T 4 .
Initiation of production to the fetus
Thyrotropin-releasing hormone (TRH) is released from the hypothalamus at 6 - 8 weeks, and thyroid-stimulating hormone (TSH) secretion from the fetal pituitary gland is evident with 12 weeks gestation, and fetal thyroxine production (T 4 ) reach clinically significant levels at 18-20 weeks. Fetal triiodothyronine (T 3 ) remained low (less than 15 ng/dL) to 30 weeks' gestation, and increased to 50 ng/dL. The independence of the fetus from the thyroid hormone protects the fetus against for example. disorders of brain development caused by maternal hypothyroidism.
Influence of iodine deficiency in thyroid hormone synthesis
If there is a lack of dietary iodine, the thyroid will not be able to make thyroid hormone. Lack of thyroid hormone will cause a decrease in negative feedback on the pituitary, leading to increased production of thyroid stimulating hormone, which causes the thyroid to enlarge (the resulting medical condition is called colloid of endemic goitre ; see goiter). It has the effect of increasing the ability of the thyroid to trap more iodides, compensate for iodine deficiency and allow it to produce sufficient amount of thyroid hormone.
Circulation and transport
Plasma transport
Most of the thyroid hormones circulating in the blood are bound to "transport proteins". Only a small part of the hormone is free circulating (unbound) and biologically active, then measuring the concentration of free thyroid hormone is a great diagnostic value.
When the thyroid hormone is bound, it is inactive, so the amount of T 3 /T 4 free is important. For this reason, measuring total thyroxine in the blood can be misleading.
Although lipophilic, T 3 and T 4 cross the cell membrane through a carrier-mediated transport, which is ATP dependent.
T 1 a and T 0 a positively charged and not passing through the membrane; they are believed to function through receptors associated with the TAAR1 (TAR1, TA1) amine, the G-protein-coupled receptor located in the cell membrane.
Another important diagnostic tool is measuring the amount of thyroid-stimulating hormone (TSH) present.
Membrane transport
Contrary to popular belief, thyroid hormones can not cross cell membranes in a passive way like other lipophilic substances. Iodine in o -position makes the OH-phenolic group more acidic, produces a negative charge at physiological pH. However, at least 10 genetically regulated, energy-dependent iodothyronine transporters have been identified in humans. They ensure that intracellular thyroid hormone levels are higher than in blood plasma or interstitial fluid.
Intracellular transport
Little is known about the intracellular kinetics of thyroid hormones. However, it can be shown recently that CRYM crystallin binds 3.5.3? -triiodothyronine in vivo.
Action mechanism
Thyroid hormones function through a well-studied set of nuclear receptors, called thyroid hormone receptors. These receptors, together with the corepressor molecules, bind to the DNA regions called thyroid hormone response elements (TREs) near the genes. This receptor-corepressor-DNA complex can block gene transcription. When triiodothyronine (T3) binds to the receptor, it induces conformational change in the receptor, replacing the corepressor of the complex. This leads to the recruitment of coactivator proteins and RNA polymerase, activating gene transcription. Although this general functional model has experimental support, there are still many open-ended questions.
Thyroxine, iodine and apoptosis
Thyroxine and iodine stimulate spectacular apoptosis of larvae, tail and fins cells in amphibian metamorphosis, and stimulate the evolution of their nervous system that alters agate, vegetarian tadpoles into terrestrial and carnivorous frogs. In fact, the amphibian frog Xenopus laevis serves as an ideal model system for studying the mechanism of apoptosis.
Triiodothyronine effect
The effects of triiodothyronine (T 3 ) which is a metabolically active form:
- Increases cardiac output
- Increases heart rate
- Increase ventilation rate
- Increase basal metabolic rate
- Potentiates catecholamine effects (ie increases sympathetic activity)
- Potential brain development
- Thicken endometrium in women
- Increase protein and carbohydrate catabolism
Measurement
Thyroxine and triiodothyronine can be measured as free thyroxine and free triiodothyronine , which is an indicator of the activity of thyroxine and triiodothyronine in the body. They can also be measured as total thyroxine and total triiodothyronine, which also depend on thyroxine and triiodothyronine bound to thyroxine binding globulin. The related parameter is the free thyroxine index, which is the total thyroxine multiplied by the taking of the thyroid hormone, which, in turn, is a measure of unbound bonded thyroxine bonding globulin. In addition, thyroid disorders can be detected before birth using advanced imaging techniques and testing fetal hormone levels.
Related diseases
The advantages and disadvantages of thyroxine can cause disorders.
- Hyperthyroidism (eg Graves Disease) is a clinical syndrome caused by excess of circulating free thyroxine, free triiodothyronine, or both. This is a common disorder affecting about 2% of women and 0.2% of men. Thyrotoxicosis is often used interchangeably with hyperthyroidism, but there are subtle differences. Although thyrotoxicosis also refers to elevated circulating thyroid hormones, this may be due to intake of thyroxine tablets or by overactive thyroid, whereas hyperthyroidism refers only to overactive thyroid.
- Hypothyroidism (eg Hashimoto's thyroiditis) is a case where there is a shortage of thyroxine, triiodothyronine, or both.
- Clinical depression can sometimes be caused by hypothyroidism. Several studies have shown that T 3 is found at the synaptic junction, and regulates the amount and activity of serotonin, norepinephrine, and the -aminobutyric acid (GABA) in the brain.
- Hair loss can sometimes be associated with damage to T 3 and T 4 . The normal hair growth cycle can be affected to interfere with hair growth.
Premature birth can suffer from neurodevelopmental disorders due to lack of maternal thyroid hormones, when their own thyroid can not meet their postnatal needs. Also in normal pregnancy, maternal thyroid hormone levels are adequate to ensure the availability of thyroid hormones for the fetus and brain development. Congenital hypothyroidism occurs in every 1 of 1600-3400 newborns with most are born without symptoms and develop related symptoms weeks after birth.
Anti-thyroid medicine
Iodine uptake to concentration gradient is mediated by sodium-iodine symporter and associated with sodium-potassium ATPase. Perchlorate and thiocyanate are drugs that can compete with iodine at this point. Compounds such as goitrin, carbimazole, methimazole, propylthiouracil can reduce the production of thyroid hormones by disrupting the oxidation of iodine. thiocyanide & amp; perchlorate is used as an ionic inhibitor in anti thyroid compounds
See also
- Goitre
- Graves-Basedow Disease
- Hashimoto's thyroiditis
- Hormones
- Polar T3 syndrome
- Thyroid gland
- Thyroid stimulating hormone
- Thyronamines, thyroid hormone metabolites acting on a TAAR1 (TAR1) amine-related receptor
References
External links
- Find TH response element in DNA sequence.
- Triiodothyronine is bound to proteins in GDP
- Thyroxine is bound to proteins in GDP
- T4 in the Online Test Lab
Thyroid hormone therapy in thyroid disease
- Thyroid Hormone Treatment Brochure by American Thyroid Association
- Thoughtful article about thyroid drug use Written by MD
- Thyroid Disease Managers A collection of complicated medical articles about thyroid disease, including information about thyroid hormone
Source of the article : Wikipedia
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