Thyroid hormone
Encyclopedia
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
(T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....
(T3), are tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
-based hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
. The major form of thyroid hormone in the blood is thyroxine (T4), which has a longer half-life than T3. The ratio of T4 to T3 released into the blood is roughly 20 to 1. Thyroxine is converted to the active T3 (three to four times more potent than T4) within cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s by deiodinase
Deiodinase
Iodothyronine deiodinases are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine , the precursor of 3,5,3’-triiodothyronine is transformed into T3 by deiodinase activity. T3, through binding a nuclear thyroid hormone receptor,...
s (5'-iodinase). These are further processed by decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
and deiodination to produce iodothyronamine (T1a) and thyronamine
Thyronamine
Thyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylated and deiodinated metabolites of the thyroid hormones thyroxine and 3,5,3'-triiodothyronine .-Types:The group includes:* Thyronamine...
(T0a).
Plasma transport
Most of the thyroid hormone circulating in the bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
is bound to transport protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. Only a very small fraction of the circulating hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.
When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
can be misleading.
| bound to thyroxine-binding globulin
Thyroxine-binding globulin
Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...
(TBG)
| bound to transthyretin
Transthyretin
Transthyretin is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine and retinol binding protein bound to retinol. This is how transthyretin gained its name, transports thyroxine and retinol...
or "thyroxine-binding prealbumin" (TTR or TBPA)
| paraalbumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
| unbound T4 (fT4)
| unbound T3 (fT3)
T3 and T4 cross the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
easily as they are lipophilic molecules, and function via a well-studied set of nuclear
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
in the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
of the cell, the thyroid hormone receptor
Thyroid hormone receptor
The thyroid hormone receptor is a type of nuclear receptor that is activated by binding thyroid hormone.-Function:Amongst the most important functions of thyroid hormone receptors are regulation of metabolism and heart rate...
s.
T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor
Trace amine-associated receptor
Trace amine-associated receptors, abbreviated TAAR and otherwise known as trace amine receptors, abbreviated TAR or TA, are a class of G protein-coupled receptors identified in 2001....
(TAR1, TA1), a G-protein-coupled receptor located in the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
.
Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
(TSH) that is present.
Membrane transport
Thyroid hormones are lipophilicLipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...
substances that are able to traverse cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s even in a passive manner. However, at least 10 different active, energy dependent and genetic regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than in blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
or interstitial fluids.
Intracellular transport
Little is known about intracellular kinetics of thyroid hormones. However, recently it could be demonstrated that the crystallinCrystallin
In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors....
CRYM
CRYM
Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein is a protein that in humans is encoded by the CRYM gene. Multiple alternatively spliced transcript variants have been found for this gene.- Function :...
binds 3,5,3′-triiodothyronine in vivo.
Function
The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rateBasal metabolic rate
Basal Metabolic Rate , and the closely related resting metabolic rate , is the amount of daily energy expended by humans and other animals at rest. Rest is defined as existing in a neutrally temperate environment while in the post-absorptive state...
, affect protein synthesis, help regulate long bone growth (synergy with growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
) and neuronal maturation, and increase the body's sensitivity to catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
s (such as adrenaline) by permissiveness
Permissiveness (biology)
In biology, permissiveness is a certain relationship between hormones and the target cell. It can be applied to describe situations in which the presence of one hormone, at a certain concentration, is required in order to allow a second hormone to fully affect the target cell...
. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
, fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
, and carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, affecting how human cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
Thyroid hormone leads to heat generation in humans. However, the thyronamines function via some unknown mechanism to inhibit neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al activity; this plays an important role in the hibernation
Hibernation
Hibernation is a state of inactivity and metabolic depression in animals, characterized by lower body temperature, slower breathing, and lower metabolic rate. Hibernating animals conserve food, especially during winter when food supplies are limited, tapping energy reserves, body fat, at a slow rate...
cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.
Related diseases
Both excess and deficiency of thyroxine can cause disorders.- HyperthyroidismHyperthyroidismHyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
(an example is Graves Disease) is the clinical syndrome caused by an excess of circulating free thyroxine, free triiodothyronine, or both. It is a common disorder that affects approximately 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 an increase in circulating thyroid hormones, it can be caused by the intake of thyroxine tablets or by an over-active thyroid, whereas hyperthyroidism refers solely to an over-active thyroid. - HypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(an example is Hashimoto's thyroiditisHashimoto's thyroiditisHashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both. - Clinical depressionClinical depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
can sometimes be caused by hypothyroidism. Some research has shown that T3 is found in the junctions of synapseChemical synapseChemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
s, and regulates the amounts and activity of serotoninSerotoninSerotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, and Gamma-aminobutyric acidGamma-aminobutyric acidγ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system...
(GABA) in the brainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
Preterm births can suffer neurodevelopmental disorders due to lack of maternal thyroid hormones, at a time when their own thyroid is unable to meet their postnatal needs.
Measurement
Thyroxine and triiodothyronine can be measured as free thyroxine and free triiodothyronine, which are indicators of thyroxine and triiodothyronine activities in the body. They can also be measured as total thyroxine and total triiodothyronine, which also depend on the thyroxine and triiodothyronine that is bound to thyroxine-binding globulinThyroxine-binding globulin
Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...
. A related parameter is the free thyroxine index, which is total thyroxine multiplied by thyroid hormone uptake, which, in turn, is a measure of the unbound thyroxine-binding globulins.
Medical use of thyroid hormones
Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
). They are both absorbed well by the gut, so can be given orally. Levothyroxine
Levothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...
, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine (t4 only), which is metabolised more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, also under the commercial name Armour Thyroid, are derived from pig thyroid glands, and are a "natural" hypothyroid treatment containing 20% T3 and traces of T2, T1 and calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
.
Also available are synthetic combinations of T3/T4 in different ratios (such as Thyrolar) and pure-T3 medications (Cytomel).
Levothyroxine
Levothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...
is usually the first course of treatment tried. Some patients feel they do better on Armour Thyroid, though no clinical trials have shown any benefit over the biosynthetic forms.
Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia
Hypothermia
Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...
, which causes the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
to enter a protective cycle, useful in preventing damage during ischemic shock
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
.
Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger
George Barger
George Barger FRS was a British chemist.He was born to an English mother and Dutch father in Manchester, England. He was educated at The Hague High School and King's College, Cambridge. His main work focused on the study of alkaloids and investigations of simple nitrogenous compounds of biological...
in 1926.
Formulations
Today most patients are treated with levothyroxine, or a similar synthetic thyroid hormone. However, natural thyroid hormone supplementsDesiccated thyroid extract
Desiccated thyroid or thyroid extract, refers to porcine thyroid glands, dried and powdered for therapeutic use. As an animal product, it is not suitable for use by vegetarians. Some religious dietary laws object to the use of pork products as well, although exceptions are sometimes made for...
from the dried thyroids of animals are still available. Natural thyroid hormones have become less popular, mostly due to rumors that varying hormone concentrations in the thyroids of animals before they are slaughtered leads to inconsistent potency and stability. However natural products mix thyroid powder from multiple lots and perform analytical tests to insure strict compliance with FDA standards, and it has actually been the synthetic thyroid hormone that has shown a consistent history of potency or stability problems. Levothyroxine contains T4 only and is therefore largely ineffective for patients unable to convert T4 to T3. These patients may choose to take natural thyroid hormone as it contains a mixture of T4 and T3, or alternatively supplement with a synthetic T3 treatment. Some natural thyroid hormone brands are F.D.A. approved, but some are not. Thyroid hormones are generally well tolerated. Thyroid hormones are usually not dangerous for pregnant women or nursing mothers, but should be given under a doctor's supervision. In fact, if a woman who is hypothyroid is left untreated, her baby is at a higher risk for birth defects. When pregnant, a woman with a low functioning thyroid will also need to increase her dosage of thyroid hormone.. One exception is that thyroid hormones may aggravate heart conditions, especially in older patients; therefore, doctors may start these patients on a lower dose & work up to avoid risk of heart attack.
Central
Thyroid hormones (T4 and T3) are produced by the follicular cellThyroid epithelial cell
Thyroid epithelial cells are cells in the thyroid gland that are responsible for the production and secretion of thyroid hormones, that is, thyroxine and triiodothyronine .-Function:...
s of the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
gland and are regulated by TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
made by the thyrotrophs
Thyrotrope
Thyrotropes are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone in response to thyrotropin releasing hormone .Thyrotropes appear basophilic in histological preparations....
of the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
gland. Because the effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues), T3 is 3- to 5- fold more active than T4.
Thyroxine (3,5,3',5'-tetraiodothyronine) is produced by follicular cells of the thyroid gland. It is produced as the precursor thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
(this is not the same as TBG
Thyroxine-binding globulin
Thyroxine-binding globulin binds thyroid hormone in circulation. It is one of three proteins responsible for carrying the thyroid hormones thyroxine and 3,5,3’-triiodothyronine in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest...
), which is cleaved by enzymes to produce active T4.
Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
molecules. Thyroxine (T4) contains four iodine atoms. Triiodothyronine (T3) is identical to T4, but it has one less iodine atom per molecule.
Iodide
Iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. This page is for the iodide ion and its salts. For information on organoiodides, see organohalides. In everyday life, iodide is most commonly encountered as a component of iodized salt,...
is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
is cotransported with iodide from the basolateral side of the membrane into the cell and then concentrated in the thyroid follicles to about thirty times its concentration in the blood. Via a reaction with the enzyme thyroperoxidase, iodine is bound to tyrosine residues in the thyroglobulin
Thyroglobulin
Thyroglobulin is a 660 kDa, dimeric protein produced by and used entirely within the thyroid gland. In earlier literature, Tg was referred to as colloid....
molecules, forming monoiodotyrosine
Monoiodotyrosine
Monoiodotyrosine is a precursor of thyroid hormone and results from iodization of tyrosine at the meta- position of the phenol ring.Two units can combine to form 3,3'-diiodothyronine. One unit can combine with diiodotyrosine to form triiodothyronine, as occurs in the colloid of the thyroid...
(MIT) and diiodotyrosine
Diiodotyrosine
Diiodotyrosine is a precursor of thyroid hormone and results from iodization of monoiodotyrosine at the other meta- position on the phenol ring....
(DIT). Linking two moieties of DIT produces thyroxine. Combining one particle of MIT
and one particle of DIT produces triiodothyronine.
- DIT + MIT → r-T3 (biologically inactive)
- MIT + DIT → triiodothyronine (usually referred to as T3)
- DIT + DIT → thyroxine (referred to as T4)
Proteases digest iodinated thyroglobulin, releasing the hormones T4 and T3, the biologically active agents central to metabolic regulation.
Peripheral
ThyroxineThyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
is believed to be a prohormone
Prohormone
A prohormone is a substance that is a precursor to a hormone, usually having minimal hormonal effect by itself. The term has been used in medical science since the middle of the 20th century. The primary function of a prohormone is to enhance the strength of the hormone that already occurs in the...
and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by iodothyronine deiodinase. Deficiency of deiodinase can mimic an iodine deficiency. T3 is more active than T4 and is the final form of the hormone, though it is present in less quantity than T4.
Initiation of production in fetuses
Thyrotropin-releasing hormoneThyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...
(TRH) and thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
(TSH) start being secreted from the fetal hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
and pituitary at 18-20 weeks of gestation, and fetal production of thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
(T4) reach a clinically significant level at 18–20 weeks. Fetal triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, 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....
(T3) remains low (less than 15 ng/dL) until 30 weeks of gestation, and increases to 50 ng/dL at term. Fetal self-sufficiency of thyroid hormones protects the fetus against e.g. brain development abnormalities caused by maternal hypothyroidism.
Effect of iodine deficiency on thyroid hormone synthesis
If there is a deficiency of dietary iodineIodine deficiency
Iodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...
, the thyroid will not be able to make thyroid hormone. The lack of thyroid hormone will lead to decreased negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
on the pituitary, leading to increased production of thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
, which causes the thyroid to enlarge (goiter)endemic colloid goiter. This has the effect of increasing the thyroid's ability to trap more iodide, compensating for the iodine deficiency and allowing it to produce adequate amounts of thyroid hormone.
Anti-thyroid drugs
Iodine uptake against a concentration gradient is mediated by a sodium-iodine symporter and is linked to a sodium-potassium ATPase. Perchlorate and thiocyanate are drugs that can compete with iodine at this point. Compounds such as goitrinGoitrin
Goitrin is a sulfur-containing oxazolidine, a cyclic thiocarbamate, that reduces the production of thyroid hormones such as thyroxine. It is found in cruciferous vegetables such as cabbage, brussels sprouts and oil-seed rape, and is formed by the hydrolysis of a glucosinolate; 2-hydroxy-3-butenyl...
can reduce thyroid hormone production by interfering with iodine oxidation.
Effects of thyroxine
- Increases cardiac outputCardiac outputCardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
- Increases heart rate
- Increases ventilation rate
- Increases basal metabolic rateBasal metabolic rateBasal Metabolic Rate , and the closely related resting metabolic rate , is the amount of daily energy expended by humans and other animals at rest. Rest is defined as existing in a neutrally temperate environment while in the post-absorptive state...
- Potentiates the effects of catecholamines (i.e. increases sympathetic activity)
- Potentiates brain development
- Thickens endometriumEndometrium-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
in females - increase metabolism of proteins and carbohydrates
Herbs
There are no herbs (plant chemicals) that contain thyroid hormone. Therefore, while there are some herbs that may provide some help for a sluggish thyroid (i.e. if the thyroid is producing a low amount of thyroid hormone, but has not stopped completely), myxedema requires treatment with synthetic or desiccated natural thyroid hormones. However, there are many edible plants that have high concentrations of iodine (e.g., seaweed and kelp). Iodine is an irreplaceable precursor to the biosynthesis of thyroid hormones.See also
- HormoneHormoneA hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
- ThyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
gland - Thyroid-stimulating hormoneThyroid-stimulating hormoneThyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
- ThyronamineThyronamineThyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylated and deiodinated metabolites of the thyroid hormones thyroxine and 3,5,3'-triiodothyronine .-Types:The group includes:* Thyronamine...
s, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1 (TAR1) - GoitreGoitreA goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
- Graves-Basedow diseaseGraves-Basedow diseaseGraves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...
External links
Thyroid hormone treatment in thyroid disease
Thyroid disease
-Hyper- and hypofunction:Imbalance in production of thyroid hormones arises from dysfunction of the thyroid gland itself, the pituitary gland, which produces thyroid-stimulating hormone , or the hypothalamus, which regulates the pituitary gland via thyrotropin-releasing hormone . Concentrations of...
- Thyroid Hormone Treatment Brochure by the American Thyroid Association
- Elaborate article about the use of thyroid drugs Written by an MD
- What is the "Best" Thyroid Drug? Is it Synthroid, Unithroid, Armour, Thyrolar, or Something Else? Article by health activist and patient advocate Mary ShomonMary ShomonMary Shomon, born 1961, is an American health activist and author whose primary focus is thyroid disease.-Published work:She is the author of one New York Times best-selling book, The Thyroid Diet: Manage Your Metabolism for Lasting Weight Loss, published by Harper Collins in 2004, along with a...
- Thyroid Disease Manager Collection of elaborate medical articles on thyroid disease, including information on thyroid hormones
- Stop the thyroid madness Collection of references to articles comparing different treatment methods of hypothyroidism