Monday, April 30, 2012

Thyroid Hormones

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. The major form of thyroid hormone in the blood is thyroxine (T4). 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 cells by the deiodinases enzyme (5'-iodinase). These are further processed by decarboxylation and deiodination to produce iodothyronamine (T1a) and thyronamine (T0a).
 
Synthetic thyroxine was first successfully produced by Charles Robert Harington and George Barger in 1926.
 
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 is not active, so the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.T3 and T4 cross the cell membrane, and function via a well-studied set of nuclear receptors in the cell nucleus.T1a and T0a are positively charged and do not cross the membrane; they are believed to function via the trace amine-associated receptor TAAR1 (TAR1, TA1), a G-protein-coupled receptor located in the cell membrane.
 
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. Numerous physiological and pathological stimuli influence thyroid hormone synthesis.
 
Related diseases
Both excess and deficiency of thyroxine can cause disorders.

  • Thyrotoxicosis or hyperthyroidism (more specifically 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 (an example is Hashimoto's thyroiditis) is the case where there is a deficiency of thyroxine, triiodiothyronine, or both.
  • Clinical depression can sometimes be caused by hypothyroidism. Some researchhas shown that T3 is found in the junctions of synapses, and regulates the amounts and activity of serotonin, norepinephrine, and Gamma-aminobutyric acid (GABA) in the brain.
 
Medical use of thyroid hormones
Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both can be given oraly and ar absorbed well by the gut. Levothyroxine, the most commonly used synthetic thyroxine form, is a stereoisomer of physiological thyroxine, which is metabolized more slowly and hence usually only requires 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.
 
Production of the thyroid hormones
Thyroxine (3,5,3',5'-tetra iodothyronine) 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 T4.Thyroxine is produced by attaching iodine atoms to the ring structures of tyrosine molecules. Thyroxine (T4) contains four iodine atoms. Triiodothyronine (T3) is identical to T4, 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 is 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.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 is present in less quantity than T4.

B.”EvilGenius”Chavez                                                                                                                                              EvilGenius Sports Performance www.EvilGSP.com