Medicine

T3 increases the basal metabolic rate and thus increases the body’s oxygen and energy consumption. The basal metabolic rate is the minimal caloric requirement needed to sustain life in a resting individual. T3 acts on the majority of tissues within the body, with a few exceptions including the spleen and testis. It increases the production of the Na+/K+ -ATPase and in general increases the turnover of different endogenous macromolecules by increasing their synthesis and degradation.

Protein
T3 stimulates the production of RNA Polymerase I and II and therefore increases the rate of protein synthesis. It also increases the rate of protein degradation and in excess the rate of protein degradation exceeds the rate of protein synthesis. In such situations the body may go into negative ion balance.

Glucose
T3 potentiates the effects of the β-adrenergic receptors on the metabolism of glucose. It therefore increases the rate of glycogen breakdown and glucose synthesis in gluconeogenesis. It also potentiates the effects of insulin, which have opposing effects.

Lipids
T3 stimulates the breakdown of cholesterol and increases the number of LDL receptors, therefore increasing the rate of lipolysis.

T3 also affects the cardiovascular system. It increases the cardiac output by increasing the heart rate and force of contraction. This results in increased systolic blood pressure and decreased diastolic blood pressure. The latter two effects act to produce the typical bounding pulse seen in hyperthyroidism.

T3 also has profound effect upon the developing embryo and infants. It affects the lungs and influences the postnatal growth of the central nervous system. It stimulates the production of myelin, neurotransmitters and axon growth. It is also important in the linear growth of bones.

T3 and T4 are carried in the blood bound to plasma proteins. This has the effect of increasing the half life of the hormone and decreasing the rate at which it is taken up by peripheral tissues. There are three main proteins that the two hormones are bound to. Thyronine binding globulin (TBG) is a gylcoprotein that has a higher affinity for T4 than for T3. The second plasma protein to which the hormone bind is transthyretin (which has a higher affinity for T3 than for T4). Both hormones bind with a low affinity to serum albumin, but due to the large availability of albumin it has a high capacity.

The T3 (and T4) bind to nuclear receptors, thyroid receptors. However, T3 (and T4) are not very lipophilic and as a result, are unable to pass through the phospholipid bilayers. They therefore have specific transport proteins on the cell membranes of the effector organs which allow the T3 and T4 to pass into the cells. The thyroid receptors bind to response elements in gene promoters and thus enabling them to activate or inhibit transcription. The sensitivity of a tissue to T3 is modulated through the thyroid receptors.

T3 is metabolically active hormone that is produced from T4. T4 is deiodinated by two deiodinases to produce the active triiodothyronine:
1. Type I present within the liver and accounts for 80% of the deiodination of T4
2. Type II present within the pituitary.

T4 is synthesised in the thyroid gland follicular cells as follows.
1. The Na+/I- symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is secondary active transporter that utilises the concentration gradient of Na+ to move I- against its concentration gradient.
2. I- is moved across the apical membranae into the colloid of the follicle.
3. Thyroperoxidase oxidises two I- to form I2. Iodide is non-reactive and only the more reactive iodine is required for the next step.
4. The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.
5. Thyroid stimulating hormone (TSH) released from the pituitary gland binds the TSH receptor ( a Gs protein coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
6. The endosytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.
7. These vesicles are then exocytosed releasing the thyroid hormones.

In the follicular lumen, tyrosine residues become iodinated. This reaction requires hydrogen peroxide. Iodine bonds carbon 3 or carbon 5 of tyrosine residues of thyroglobulin in a process called organification of iodine. The iodination of specific tyrosines yields monoiodotyrosine (MIT) and diiodotyrosine (DIT). One MIT and one DIT are enzymatically coupled to form T3. The enzyme is thyroid peroxidase.

Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone.

Thyroid-stimulating hormone (TSH) activates the production of thyroxine (T4) and T3. This process is under regulation. In the thyroid, T4 is converted to T3. TSH is inhibited mainly by T3. The thyroid gland releases greater amounts of T4 than T3, so plasma concentrations of T4 are 40-fold higher than those of T3. Most of the circulating T3 is formed peripherally by deiodination of T4 (85%), a process that involves the removal of iodine from carbon 5 on the outer ring of T4. Thus, T4 acts as prohormone for T3.

This thyroid hormone is similar to thyroxine but with one fewer iodine atoms per molecule. In addition, T3 exhibits greater activity and is produced in smaller quantity.

It is the most powerful thyroid hormone, and affects almost every process in the body, including body temperature, growth, and heart rate.

The biological halflife is 2.5 days.[1]

Thyroxine, or 3,5,3′,5′-tetraiodothyronine (often abbreviated as T4), a form of thyroid hormones is the major hormone secreted by the follicular cells of the thyroid gland. Thyroxine is synthesized via the iodination and covalent bonding of the phenyl portions of tyrosine residues found in an initial peptide, thyroglobulin, which is secreted into thyroid granules. These iodinated diphenyl compounds are cleaved from their peptide backbone upon being stimulated by thyroid stimulating hormone. More in the T3 and T4 section of thyroid.

T4 is transported in blood, with 99.95% of the secreted T4 being protein bound, principally to thyroxine-binding globulin (TBG), and, to a lesser extent, to transthyretin and serum albumin. T4 is involved in controlling the rate of metabolic processes in the body and influencing physical development. Administration of thyroxine has been shown to significantly increase the concentration of nerve growth factor in the brains of adult mice.[1]

Thyroxine is a prohormone and a reservoir for the active thyroid hormone triiodothyronine (T3) which is about four times more potent. T4 is converted in the tissues by deiodinases to T3. The “D” isomer is called “Dextrothyroxine”[2] and is used as a lipid modifying agent.[3] The half-life of thyroxine once released into the blood circulatory system is about 1 week.

The hormone was synthesised in 1927 by British chemists Charles Robert Harington and George Barger.

There are no herbs (plant chemicals) that contain thyroid hormone[7][14]. 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)[15], myxedema requires treatment with synthetic or desiccated natural thyroid hormones[16][14].

Today most patients (at least in industrialized countries) are treated with levothyroxine, or a similar synthetic thyroid hormone[4][5][6]. However, natural thyroid hormone supplements from the dried thyroids of animals are still available[6]. Natural thyroid hormones have become less popular, mostly because the concentration of thyroid hormones in the thyroids of animals before they were slaughtered naturally varies somewhat[6]. However, some people are afraid of rare allergic reactions to synthetic pharmaceuticals, and some patients & doctors just prefer natural treatments. For these people, natural thyroid treatments hormones are still available[7][6][8][9][10]. Some natural thyroid hormone brands are F.D.A. approved, but some are not[11][12][13]. Thyroid hormones are generally well tolerated[5]. Thyroid hormones are usually not dangers for pregnant women or nursing mothers, but should be given a doctor’s supervision[5]. 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 heartattack[6].

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 females

If there is a deficiency of dietary iodine, the thyroid will not be able to make thyroid hormone. The lack of thyroid hormone will lead to decreased negative feedback 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.