Everything about The Thyroid Hormone totally explained
The
thyroid hormones,
thyroxine (
T4) and
triiodothyronine (
T3), are
tyrosine-based
hormones produced by the
thyroid gland. An important component in the synthesis is
iodine. The major form of thyroid hormone in the blood is thyroxine (T
4). The ratio of T
4 to T
3 released in the blood is roughly 20 to 1. Thyroxine is converted to the active T
3 (three to four times more potent than T
4) within
cells by
deiodinases (5'-iodinase). These are further processed by
decarboxylation and deiodination to produce
iodothyronamine (
T1a) and
thyronamine (
T0a).
Circulation
Most of the thyroid hormone circulating in the
blood is bound to transport
proteins. Only a very small fraction of the circulating
hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.
When thyroid hormone is bound, it isn't active, so the amount of free T
3/T
4 is what is important. For this reason, measuring total
thyroxine in the
blood can be misleading.
T
3 and T
4 cross the
cell membrane, probably via amino acid
importins, and function via a well-studied set of
nuclear receptors in the
nucleus of the cell, the
thyroid hormone receptors.
T
1a and T
0a are positively charged and don't cross the membrane; they're believed to function via the
trace amine-associated receptor (TAR1, TA1), a
G-protein-coupled receptor located in the
cell membrane.
Another critical diagnostic tool is the amount of
thyroid-stimulating hormone (TSH) that's present.
Function
The thyronines act on the body to increase the
basal metabolic rate, affect
protein synthesis and increase the body's sensitivity to
catecholamines (such as
adrenaline) by
permissiveness. The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate
protein,
fat, and
carbohydrate metabolism, affecting how human
cells use energetic compounds. They also stimulate vitamin metabolism. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
Thyroid hormone leads to heat generation in human. However, the
thyronamines function via some unknown mechanism to inhibit
neuronal activity; this plays an important role in the
hibernation 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.
Medical use of thyroid hormones
Both T
3 and T
4 are used to treat thyroid hormone deficiency (
hypothyroidism). They are both absorbed well by the gut, so can be given orally.
Levothyroxine, 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's a "natural" hypothyroid treatment containing 20% T
3 and traces of T
2, T
1 and
calcitonin.
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 which causes the
brain to enter a protective cycle, useful in preventing damage during
ischemic shock.
Synthetic thyroxine was first successfully produced by
Charles Robert Harington and
George Barger 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 (this is
not the same as
TBG), which is cleaved by enzymes to produce active T
4.
Thyroxine is produced by attaching iodine atoms to the ring structures of
tyrosine molecules. Thyroxine (T
4) contains four iodine atoms. Triiodothyronine (T
3) is identical to T
4, but it has one less iodine atom per molecule.
Iodide is actively absorbed from the bloodstream by a process called '
iodine trapping'and concentrated in the thyroid follicles. (If there's a
deficiency of dietary iodine, the thyroid enlarges in an attempt to trap more iodine, resulting in
goitre.) Via a reaction with the enzyme
thyroperoxidase, iodine is covalently bound to tyrosine residues in the
thyroglobulin 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 and a reservoir for the most active and main thyroid hormone T3. T4 is converted as required in the tissues by deiodinases. Deficiency of deiodinase can mimic an iodine deficiency. T3 is more active than T4 and is the final form of the hormone, though it's present in less quantity than T4.
Anti-thyroid drugs
Iodine uptake against a concentration gradient is mediated by a sodium iodine symporter. Perchlorate and thiocyanate are drugs that can compete with iodine at this point.
Effects of thyroxine
Increases cardiac output
Increases heart rate
Increases ventilation rate
Increases basal metabolic rate
Potentiates the effects of catecholamines (i.e increases sympathetic activity)
Potentiates brain development
Thickens endometrium in femalesFurther Information
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