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The thyroid hormones, thyroxine
Thyroxine

Thyroxine, or 3,5,3',5'-tetra?iodothyronine , a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland....
 (T4) and triiodothyronine
Triiodothyronine

Triiodothyronine, carbonhydrogeniodinenitrogenoxygen, also known as T3, is a thyroid hormone.Thyroid-stimulating hormone activates the production of thyroxine and T3....
 (T3), are tyrosine
Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
-based hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
s produced by the thyroid gland.






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T4 3d Vdw
T3 3d Vdw
The thyroid hormones, thyroxine
Thyroxine

Thyroxine, or 3,5,3',5'-tetra?iodothyronine , a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland....
 (T4) and triiodothyronine
Triiodothyronine

Triiodothyronine, carbonhydrogeniodinenitrogenoxygen, also known as T3, is a thyroid hormone.Thyroid-stimulating hormone activates the production of thyroxine and T3....
 (T3), are tyrosine
Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
-based hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
s produced by the thyroid gland. An important component in the synthesis of thyroid hormones is iodine
Iodine

Iodine , is a chemical element that has the symbol I and atomic number 53. Naturally-occurring iodine is a single isotope with 74 neutrons....
. 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 in 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 structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
s by deiodinase
Deiodinase

Deiodinase is an enzyme important in the action of thyroid hormones. Deiodinases are unusual in that the enzyme contains selenium, in the form of an otherwise rare amino acid selenocysteine....
s (5'-iodinase). These are further processed by decarboxylation
Decarboxylation

Decarboxylation is any chemical reaction in which a carboxyl group is split off from a compound as carbon dioxide ....
 and deiodination to produce iodothyronamine (T1a) and thyronamine
Thyronamine

Thyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylation and iodine metabolites of the thyroid hormones thyroxine and triiodothyronine ....
 (T0a).

Circulation


Most of the thyroid hormone circulating in the blood
Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
 is bound to transport protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
s. Only a very small fraction of the circulating hormone
Hormone

Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
 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'-tetra?iodothyronine , a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland....
 in the blood
Blood

Blood is a specialized bodily fluid that delivers necessary substances to the body's Cell s ? such as nutrients and oxygen ? and transports waste products away from those same cells....
 can be misleading.

Type Percent >- | 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....
 (TBG)		- | bound to transthyretin
Transthyretin

Transthyretin is a blood plasma and cerebrospinal fluid carrier of the thyroid hormone thyroxine .TTR was originally called prealbumin because it ran faster than albumins on electrophoresis gels....
 or "thyroxine-binding prealbumin" (TTR or TBPA) 		- | paraalbumin
Serum albumin

Serum albumin, often referred to simply as albumin, is the most abundant plasma protein in humans and other mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular compartments and body tissues....
 		- | unbound T4 (fT4) - | unbound T3 (fT3) 0.3%


T3 and T4 cross the cell membrane
Cell membrane

The cell membrane is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
, probably via amino acid importins, 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 the interior of cells that are responsible for sensing the presence of hormone and certain other molecules....
 receptors
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
 in the nucleus
Cell nucleus

In cell biology, the nucleus , also sometimes referred to as the "control center", is a membrane-enclosed organelle found in all eukaryote cell ....
 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....
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 and 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 is the interface between the cellular machinery inside the cell and the fluid outside.It is a semipermeable lipid bilayer found in all cell ....
.

Another critical diagnostic tool is measurement of the amount of thyroid-stimulating hormone
Thyroid-stimulating hormone

Thyroid-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....
 (TSH) that is present.

Function


The thyronines act on nearly every cell in the body. They act to increase the basal metabolic rate
Basal metabolic rate

Basal metabolic rate is the amount of energy expended while at rest in a neutrally temperate environment, in the post-absorptive state . The release of energy in this state is sufficient only for the functioning of the vital organs, such as the heart, lungs, brain and the rest of the nervous system, liver, kidneys, sex organs, muscles and sk...
, affect protein synthesis
Protein synthesis

Protein synthesis is the creation of proteins using DNA and RNA. Proteins can often be synthesized directly from genes by Translation mRNA. When a protein is harmful and needs to be available on short notice or in large quantities, a protein precursor is produced....
, help regulate long bone growth (synergy with growth hormone
Growth hormone

Growth hormone is a peptide hormone. It stimulates human development and cell reproduction in humans and other animals. It is a 191-amino acid, single chain polypeptide hormone which is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland....
), neuronal maturation and increase the body's sensitivity to catecholamine
Catecholamine

Catecholamines are chemical compounds derived from the amino acid tyrosine. Their name is derived from the fact that they contain catechol and amine moieties....
s (such as adrenaline) by permissiveness
Permissiveness (biology)

In biology, permissiveness refers to 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 organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
, fat
Fat

Fats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water. Chemistry, fats are generally ester of glycerol and fatty acids....
, and carbohydrate
Carbohydrate

Carbohydrates or saccharides are the most abundant of the four major classes of biomolecules. They fill numerous roles in living things, such as the storage and transport of energy and structural components ....
 metabolism
Metabolism

Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments....
, affecting how human cell
Cell (biology)

The cell is the structural and functional unit of all known Life organisms. It is the smallest unit of an organism that is classified as living, and is often called the building bricks of life....
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

Neurons are responsive cell in the nervous system that process and transmit information by electrochemical Signal . They are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves....
al activity; this plays an important role in the hibernation
Hibernation

Hibernation is a state of inactivity and Metabolism depression in animals, characterized by lower body temperature, slower breathing, and lower metabolic 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.

  • Thyrotoxicosis or hyperthyroidism
    Hyperthyroidism

    Hyperthyroidism is the term for overactive tissue within the thyroid gland,resulting in overproduction and thus an excess of circulating free thyroid hormones: thyroxine , triiodothyronine , or both....
     (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.
  • Hypothyroidism
    Hypothyroidism

    Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
     (an example is Hashimoto's thyroiditis
    Hashimoto's thyroiditis

    Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease where the body's own T-cells attack the cell s of the thyroid....
    ) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
  • Clinical depression
    Clinical depression

    Major depressive disorder is a mental disorder characterized by a pervasive depression , low self-esteem, and anhedonia in normally enjoyable activities....
     can sometimes be caused by hypothyroidism. Some research has shown that T3 is found in the junctions of synapse
    Chemical synapse

    Chemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in neuromuscular junctions or glands....
    s, and regulates the amounts and activity of serotonin
    Serotonin

    Serotonin is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system and enterochromaffin cells in the gastrointestinal tract of animals including humans....
    , norepinephrine
    Norepinephrine

    Norepinephrine or noradrenaline is a catecholamine with dual roles as a hormone and a neurotransmitter.As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled....
    , and Gamma-aminobutyric acid
    Gamma-aminobutyric acid

    γ-Aminobutyric acid is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays an important role in regulating neuronal excitability throughout the nervous system....
     (GABA) in the brain
    Brain

    The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as cnidarian and echinoderm have a decentralized nervous system without a brain, while sponges lack any nervous system at all....
    .


Medical use of thyroid hormones


Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism
Hypothyroidism

Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants....
). They are both absorbed well by the gut, so can be given orally. Levothyroxine
Levothyroxine

levothyroxine, also L-thyroxine, synthetic thyroxine, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine ....
, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine, which is metabolised more slowly and hence usually only needs once-daily administration. Natural desiccated thyroid hormones, also under the commercial name Armour Thyroid, is derived from pig thyroid glands, it is 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 cell cells of the thyroid, and in many other animals in the ultimobranchial body....
. Also available are synthetic combinations of T3/T4 in different ratios (such as Thyrolar) and pure-T3 medications (Cytomel).

Thyronamines have no medical usages yet, though their use has been proposed for controlled induction of hypothermia
Hypothermia

Hypothermia is a condition in which an organism's temperature drops below that required for normal metabolism and bodily functions. In warm-blooded animals, core body temperature is maintained near a constant level through biologic homeostasis....
 which causes the brain
Brain

The brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as cnidarian and echinoderm have a decentralized nervous system without a brain, while sponges lack any nervous system at all....
 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....
.

Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger
George Barger

George Barger was a chemist. He was born to an English mother and Dutch father in Manchester, England. His main work focused on the study of alkaloids and investigations of simple nitrogenous compounds of biological importance....
 in 1926.

Production of the thyroid hormones


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....
), 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 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
 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 an iodine with a −1 electric charge. Compounds with iodine in formal oxidation state −1 are called iodides. This can include ionic compounds such as caesium iodide or covalent compounds such as phosphorus triiodide....
 is actively absorbed from the bloodstream by a process called iodide trapping. In this process, sodium
Sodium

Sodium is an element which has the symbol Na , atomic number 11, atomic mass 23 amu , and a common oxidation number +1. Sodium is a soft, silvery white, highly reactive element and is a member of the alkali metals within "group 1" ....
 is cotransported with iodide from the apical 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 covalently 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 (MIT) and diiodotyrosine (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. Thyroxine is supposedly 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....
 and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by deiodinase
Deiodinase

Deiodinase is an enzyme important in the action of thyroid hormones. Deiodinases are unusual in that the enzyme contains selenium, in the form of an otherwise rare amino acid selenocysteine....
s. 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.

Effect of iodine deficiency on thyroid hormone synthesis

If there is a deficiency of dietary iodine
Iodine 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 inland...
, 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 feeds part of a system's output, inverted, into the system's input; generally with the result that fluctuations are attenuated....
 on the pituitary, leading to increased production of thyroid stimulating hormone, which causes the thyroid to enlarge (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 goitrin
Goitrin

Goitrin is an sulfur-containing oxazolidine that reduces the production of thyroid hormones such as thyroxine. It is found in cruciferous vegetables such as cabbage and brussels sprouts and oil-seed rape, and is formed by the hydrolysis of glucosinolates....
 can reduce thyroid hormone production by interfering with iodine oxidation.

Effects of thyroxine

  • Increases cardiac output
    Cardiac output

    Cardiac output is the volume of blood being pumped by the heart, in particular by a ventricle in a minute. This is measured in dm3 min-1 ....
  • Increases heart rate
  • Increases ventilation rate
  • Increases basal metabolic rate
    Basal metabolic rate

    Basal metabolic rate is the amount of energy expended while at rest in a neutrally temperate environment, in the post-absorptive state . The release of energy in this state is sufficient only for the functioning of the vital organs, such as the heart, lungs, brain and the rest of the nervous system, liver, kidneys, sex organs, muscles and sk...
  • Potentiates the effects of catecholamines (i.e increases sympathetic activity)
  • Potentiates brain development
  • Thickens endometrium
    Endometrium

    The endometrium is the inner membrane of the mammalian uterus....
     in females


See also

  • Hormone
    Hormone

    Hormones are chemicals released by cells that affect cells in other parts of the body. Only a small amount of hormone is required to alter cell metabolism....
  • Thyroid
    Thyroid

    The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck inferior to the thyroid cartilage and at approximately the same level as the cricoid cartilage....
     gland
  • Thyroid-stimulating hormone
    Thyroid-stimulating hormone

    Thyroid-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....
  • Thyronamine
    Thyronamine

    Thyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylation and iodine metabolites of the thyroid hormones thyroxine and triiodothyronine ....
    s, metabolites of the thyroid hormones that act at the trace amine-associated receptor TAAR1 (TAR1)
  • Goitre
    Goitre

    A goitre , or goiter , also called a bronchocele, is a swelling in the neck due to an enlarged thyroid....
  • Graves-Basedow disease
    Graves-Basedow disease

    Graves' disease is a thyroid disorder characterized by Goitre, exophthalmos, "orange-peel" skin, and hyperthyroidism. It is caused by an antibody-mediated auto-immune reaction, but the trigger for this reaction is still unknown....


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