Protein thyroid

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

SchusslerGC. 2000. Tlie thyroxine-binding proteins. Thyroid 10 141-149. 

The steroid hormones act on cytoplasmic receptors, and the resulting complex moves to the nucleus to influence DNA transcription of proteins. Thyroid hormone directly enters the nucleus where it alters DNA, causing production of. certain enzymes. A particular chemical may have more than one receptor type (e.g., alpha and beta receptors). Epinephrine, for instance, acts on alpha-1 receptors to produce vasoconstriction, and on beta-2 receptors to produce vasodilation. 

A. Wang R, Nelson JC, Weiss RM, Wilcox RB. Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins. Thyroid 2000 10 31-9. 

Most proteins Thyroid hormones Maternal IgM, IgA Maternal and fetal erythrocytes... 

H5. Hamolsky, M. W., Stein, M., Fischer, D. B., and Freedberg, A. 8., Further studies of factors affecting the plasma protein-thyroid hormone complex. Endocrinology 68, 662-670 (1961). 

The differential diagnosis of carcinoid and atypical carcinoid tumors of the larynx includes paraganglioma, melanoma, and medullary thyroid carcinoma. Paragangliomas are rarely always negative for cyto-keratins and also exhibit the characteristic susten-tacular cell pattern with SlOO protein. Thyroid transcription factor-1 (TTEl) is positive in medullary thyroid carcinoma, as are calcitonin and CEA. Melanomas will typically stain with HMB45 and tyrosinase, both of which are negative in neuroendocrine carcinomas. 

Once thyroid hormone enters a cell, it binds temporarily with a spt plasmic protein. Thyroid hormone molecules migrate to the nucleus chondria, where they bind to receptors. In the nucleus the binding hormone initiates the transcription of genes that play crucial roles i of cellular processes, such as those that code for growth hormone a ATPase. In mitochondria, thyroid hormones promote oxygen consur increased fatty acid oxidation. (The mechanism by which this latter pro< is not understood.)... 

Hamolsky, M. W., A. Golodetz, and A. S. Freedberg. 1959. The plasma protein-thyroid hormone complex in man. IB. Further studies on the use of the in vitro red blood cell uptake of Ij3j triiodothyronine as a diagnostic test of thyroid function. Journal of Clinical Endrocrinology and Metabolism 19 101-116. 

The plasma half-life of T4 is approximately 7 days, and that of T3 is 1 to 1.5 days. These relatively long plasma half-lives result from binding of T3 and T4 to several transport proteins in the blood. Of these transport proteins, thyroid-binding globulin (TBG) has the highest affinity for these hormones and carries approximately 70% of... 

The lodothyronines secreted by the thyroid gland into thyroid vein blood are of limited solubility. They equilibrate rapidly, however, through noncovalent association with three major binding proteins thyroid binding globulin (TBG), transthyretin (TTR formerly called T4 binding prealbumin), and albumin. Thyroid... 

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

Metabolic Functions. The functions of the thyroid hormones and thus of iodine are control of energy transductions (121). These hormones increase oxygen consumption and basal metaboHc rate by accelerating reactions in nearly all cells of the body. A part of this effect is attributed to increase in activity of many enzymes. Additionally, protein synthesis is affected by the thyroid hormones (121,122). 

Only small amounts of free T are present in plasma. Most T is bound to the specific carrier, ie, thyroxine-binding protein. T, which is very loosely bound to protein, passes rapidly from blood to cells, and accounts for 30—40% of total thyroid hormone activity (121). Most of the T may be produced by conversion of T at the site of action of the hormone by the selenoenzyme deiodinase (114). That is, T may be a prehormone requiring conversion to T to exert its metaboHc effect (123). 

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Body fluids are analyzed for T and T by a variety of radioimmunoassay procedures (31) (see Immunoassays). The important clinical parameter for estimating thyroid function, the protein-bound iodine (PBI), is measured as described in treatises of clinical chemistry. High performance Hquid chromatographic (hplc) methods have replaced dc (32,33). 

Using any of the carrier proteins available in highly purified form, eg, TBG or TBPA, a convenient and accurate quantitative determination of and is possible by displacement of radioiodinated or T. This procedure enables their quick determination at low concentrations even in the presence of coundess other substances that occur in body duids (31). In a similar fashion, intact cell nuclei or solubilized proteins from rat fiver cell nuclei, which display high affinities for thyroid hormones, especially T, have been used to establish relative binding affinities of many thyromimetic compounds (7). 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

In addition to the twenty amino acids commonly found in proteins, two others—selenocysteine and pyrrolysine—are found in some organisms, and more than 700 nonprotein amino acids are also found in nature. y-Amino-butyric acid (GABA), for instance, is found in the brain and acts as a neurotransmitter homocysteine is found in blood and is linked to coronary heart disease and thyroxine is found in the thyroid gland, where it acts as a hormone. 

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

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