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Thyroxine-binding globulin

 

 
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Thyroxine-binding globulin
 
 
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Thyroxine-binding globulin (TBG) binds Thyroid hormone in circulation. It is one of three 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 (along with 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....
 and albumin
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....
) responsible for carrying the 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....
 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 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 3,5,3’-triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in serum
Blood plasma

Blood plasma is the liquid component of blood, in which the blood cells are suspended. It makes up about 55% of total blood volume. It is composed of mostly water , and contains dissolved proteins, glucose, clotting factors, mineral ions, Hormone and carbon dioxide ....
.






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Thyroxine-binding globulin (TBG) binds Thyroid hormone in circulation. It is one of three 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 (along with 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....
 and albumin
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....
) responsible for carrying the 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....
 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 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 3,5,3’-triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3, but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in serum
Blood plasma

Blood plasma is the liquid component of blood, in which the blood cells are suspended. It makes up about 55% of total blood volume. It is composed of mostly water , and contains dissolved proteins, glucose, clotting factors, mineral ions, Hormone and carbon dioxide ....
. Due to the very low serum concentration of T4 & T3, TBG is rarely more than 25% saturated with its ligand
Ligand

In chemistry, a ligand is either an atom, ion, or molecule that bonds to a central metal, generally involving formal donation of one or more of its electrons....
. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 as a 54 kDa protein. Genomically
Genomics

Genomics is the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts....
, TBG is a serpin
Serpin

Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to enzyme inhibitor proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases ....
, although it has no inhibitory function like many other members of this class of proteins.

Role in Diagnosis

TBG tests are sometimes used in finding the reason for elevated or diminished levels of thyroid hormone. This is done by measuring resin binding to labeled thyroid hormone, which only happens when the labeled thyroid hormone is free.

The patient's serum is mixed with the labeled thyroid hormone; then, the resin is added to the whole mixture, to measure the amount of free labeled thyroid hormone. So, for instance, if the patient is truly hypothyroid, and TBG levels are normal, then there are many sites open for binding on the TBG, since the total thyroid hormone level is low. Therefore, when the labeled hormone is added, it will mostly bind to the TBG, leaving little of it left for binding to the resin. Conversely, if the patient is truly hyperthyroid, and TBG levels are normal, the patient's endogenous hormone will saturate the TBG binding sites more, leaving less room for the labeled hormone, which allows greater binding to the resin.

In the situations described above, TBG testing is not very useful. However, total thyroid hormone levels point to hypothyroidism or hyperthyroidism, without the expected symptoms, the utility of TBG testing becomes more evident, since TBG production can be modified by other factors such as estrogen, corticosteroids, or liver failure. If, for example, the TBG level is high, which can occur when estrogen levels are high, the TBG will bind more thyroid hormone, decreasing the free hormone available in the blood, which leads to stimulation of TSH
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....
, and the production of more thyroid hormone. In this case, the total thyroid hormone level will be high. However, when labeled hormone is added, since TBG is so high, it will bind to the TBG, leaving little free labeled hormone for uptake into the resin. Conversely, in the presence of corticosteroids, which lower TBG levels, the total thyroid hormone (bound and free) in the blood will be low. However, when the labeled hormone is added, since so little TBG is available in the blood, only a small portion of it will bind, leaving plenty available for uptake by the resin.

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