Thyroid hormone properties

Chemical Assay. In view of the similarity of their chemical and physical properties (see Table 1) (29), the main problem in the chemical analysis of the thyroid hormones is their separation. A USP procedure gives the details of a paper chromatographic separation in which T is examined for contamination by T and 3,5-diiodothyroiiine (30). Other systems are also employed (29). 

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

Camarasa and Serra-Baldrich [94] reported allergic contact dermatitis after repeated contact with TPP-treated plastics. Meeker and Stapleton [95] indicated endocrine disruptive properties for TPP and TDCiPP, through a negative correlation with semen quality and thyroid hormone levels, respectively. Kanazawa et al. [71] associated mucosal symptoms of the sick building syndrome with high indoor exposure to TBP. These symptoms include irritation to the eyes, nose, and throat symptoms such as flushing, and mucosal symptoms such as irritation to the eyes, nose, and throat the latter symptoms were strongly associated with TBP levels in air and dust. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

Lithium has several effects on the endocrine system. For example, it can interfere with the synthesis and the release of testosterone, leading to an increase in luteinizing hormone levels. The thyroid system has been most implicated in neuroendocrine theories of lithium s antimanic effects. In particular, thyroid hormones can potentiate b-NE activity, and lithium s ability to block their release may subserve its mood-stabilizing properties (i.e., the thyroid-catecholamine receptor hypothesis)... 

Thyreostatics, also known as antihormones, are drugs capable of inhibiting the production of thyroid hormones (123). One side effect of their use is the build up of water in muscle tissues and this property has led to their illegal use in some sections of the livestock industry to increase meat yield. 

Thyrotropin alpha has the biologic properties of pituitary TSH. It binds to TSH receptors on both normal thyroid and differentiated thyroid cancer cells. The TSH-activated receptor stimulates intracellular adenylyl cyclase activity. Increased cAMP production causes increased iodine uptake and increased production of thyroid hormones and thyroglobulin. 

Several lines of evidence indicate that macromolecules of as yet unidentified chemical nature, produced by cancers and released into the systemic circulation, are responsible for the biochemical alterations in the liver and other host organs. In view of the diverse regulatory properties of the many different enzymes that increase or decrease towards their immature level (see Table III), a deficiency or excess in any given endocrine or dietary factor can clearly not explain the phenomenon. Nor has it been possible to implicate reductions in the efficacy of these factors. Subnormal concentration of the nuclear thyroid hormone receptor has been noted in the liver of tumor-bearing animals(24) however, since losses in the T3-inducible catalysts of the same liver occurred at much earlier stages of tumor-bearing,(24) the subnormal receptor concentration could clearly not be the cause of these losses but was probably another, and rather late, reflection of the process of biochemical undifferentiation. 

Typically, in gradient elution liquid chromatography, electrochemical detection has been difficult due to base-line shifts that result as a consequence of the altered mobile phase composition. However, a unique property of micelles allows for much improved compatibility of gradients (i.e. gradient in terms of micellar concentration or variation of small amount of additive such as pentanol) with electrochemical detectors. This has been demonstrated by the separation and electrochemical detection of phenols using micellar gradient LC (488). A surfactant (apparently non-micellar) gradient elution with electrochemical detection has also been successfully applied for the assay of some thyroid hormones by LC (491). 

In Table 11.2 the properties of two families of nuclear receptors, A and B, are compared. To family A belong the steroid hormone receptors and to family B, the non-steroidal receptors,25 the thyroid hormone receptors, the retinoic acid receptors, the vitamin D3 receptor, the peroxysome proliferator activating receptor, and several orphan receptors. 

Polychlorinated diphenyl ethers (PCDE) are common impurities in chlorophenol formulations, which were earlier used as fungicides, slimicides, and as wood preservatives. PCDEs are structurally and by physical properties similar to polychlorinated biphenyls (PCB). They have low water solubility and are lipophilic. PCDEs are quite resistant to degradation and are persistent in the environment. In the aquatic environment, PCDEs bioaccumulate. These compounds are found in sediment, mussel, fish, bird, and seal. PCDEs show biomagnification potential, since levels of PCDEs increase in species at higher trophic levels. PCDEs are also detected in human tissue. Despite the persistence and bio accumulation, the significance of PCDEs as environmental contaminants is uncertain. The acute toxicity and Ah-receptor-me-diated (aryl hydrocarbon) activity of PCDEs is low compared to those of polychlorinated di-benzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Due to structural similarity to thyroid hormone, PCDEs could bind to thyroid hormone receptor and alter thyroid function. Furthermore, PCDEs might be metabolized to toxic metabolites. In the environment, it is possible that photolysis converts PCDEs to toxic PCDDs and PCDFs. 

The major functions of selenium can be attributed to its antioxidative properties and its role in the regulation of thyroid hormone metabolism. Selenium is important as a nutritional factor, and the US Food and Nutrition Board s Committee on Dietary Allowances has, perhaps somewhat arbitrarily, proposed a recommended daily intake of 50-200 micrograms/day. 

Thyroglobulin. a glycoprotein, is composed of several peptide chains it also contains 0.5 to 1% iodine and 8 (o 10% carbohydrate in (he form of two types of poly.saccharide. The formation of thyroglobulin is regulated by TSH. Thyroglobulin has no hormonal properties. I( must be hydrolyzed to release the hormonal iodothyronines thyroxine and liothy-lonine (see Thyroid Hormones" in Chapter 19). 

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