Thyroid hormone biological function

Most of the physiologic activity of thyroid hormones is from the actions of T3. T4 can be thought of primarily as a prohormone. Eighty percent of needed T3 is derived from the conversion of T4 to T3 in peripheral tissue under the influence of tissue deiodinases. These deiodinases allow end organs to produce the amount of T3 needed to control local metabolic functions. These enzymes also catabolize T3 and T4 to biologically inactive metabolites. Thyroid hormones bind to intracellular receptors and regulate the transcription of various genes. 

Transport. A wellknown transport protein is hemoglobin in the erythrocytes (bottom left). It is responsible for the transport of oxygen and carbon dioxide between the lungs and tissues (see p.282). The blood plasma also contains many other proteins with transport functions. Prealbumin (transthyretin middle), for example, transports the thyroid hormones thyroxin and triiodothyronine. Ion channels and other integral membrane proteins (see p.220) facilitate the transport of ions and metabolites across biological membranes. 

In neutral and slightly alkaline media, MPO-compound I can react directly with iodides, bromides, chlorides (K16), thiocyanates, Al-acetylmethionine, cysteine, pyridine nucleotides (S20), and phenols (K16), including tyrosine (H14) and thyroid hormones. Some of these reactions have certain biological importance. In extensive studies, Klebanoff el al. investigated the potential function of MPO as an iodide-oxidizing enzyme (K16). It was found that iodide is rapidly oxidized, forming a bactericidal derivative which produces a fall in the number of viable Escherichia coli 10 times more effectively than bromide and 100 times more effectively than chloride, if used as MPO substrates. Extremely low concentrations of iodides and bromides in leukocytes and blood plasma, however, seem to limit the importance of iodide oxidation in bacteria killing mechanisms. 

Thyroid hormones have many important biological effects. A major function is their control of the basal metabolic rate and calorigenesis through increased oxygen consumption in tissue via the effects of thyroid hormone on membrane... 

Iron, the central element in oxygen transport and utilization, is discussed in Chapter 29. Iodine, a constituent of thyroid hormones, is discussed in Chapter 33. Sodium, potassium, and chloride, which are important for maintaining proper osmolality and ionic strength and for generating the electrical membrane potential, are discussed in Chapter 39. Most of this chapter is devoted to the metabolism of calcium and phosphorus because of their importance in the skeleton and other body systems. Because of its chemical and biological relationship to calcium, magnesium is also covered. The trace elements are surveyed with emphasis on those for which a biochemical function is known. 

Many hormones are members of families of related structure and reflect the prwess of molecular evolution. The steroid and thyroid hormones, which have diverse biological effects, are known now to act similarly, through one large superfamily of receptors which share structural and functional features. 

Thus, some endogenous small molecular compounds that are able to mimic the biological effect of the natural neurotrophic factors, or to stimulate their synthesis and secretion, might be promising candidates for pharmaceutical agents of various neurodegenerative diseases. Sex hormones, thyroid hormones, vitamin D and their derivatives are already known to affect survival and differentiation of dissociated mouse embryo brain in cultures or in cultured rat septal neurons. However, application of these hormones to patients with normal hormone function... 

Iodine is an essential element in humans and other mammals, which is used for the synthesis of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). These hormones play a prominent role in the metabolism of most cells of the organism and in the process of early growth and development of most organs, especially brain (Anderson et al., 2000). Besides T3 and T4, reverse T3 (rT3), monoiodotyrosine (MIT), and diiodotyrosine (DIT) are also synthesized and distributed in the body of humans and animals, but only T3 and T4 have a biological function. Iodine in the human body mainly comes through dietary and water intake, and inhalation of atmospheric iodine. Due to low concentrations of iodine in the air (10—20ng/m ), food and water intake form the major source of iodine for adults, while for infants it is milk. The concentration of iodine in foodstuffs is directly related to that in the environment where the foods come from. Iodine deficiency disorders are mainly found in places where the concentration of iodine in the soil and drinking water is very low. In the water, foodsmffs, and... 

Dioxins and dioxin-like PCBs induce a broad spectrum of toxic responses, such as loss of body mass, hepatotox-icity, immunotoxicity, epidermal changes, embryotoxicity and carcinogenicity. In addition, they can act as endocrine disrupters, thereby mimicking or interfering with the action of endogenous hormones and other molecules of the endocrine system. Besides their interference with the reproductive system, there are indications of their role in thyroid hormone (TH) metabolism and function. The toxic and biological effects of these PHAHs depend on several factors, such as doses, route of administration, species, age, strain and sex of the animals (Safe, 1986). 

Among the essential trace elements, Zn has the greatest number and variety of functions in hundreds of enzymes. In spite of the fact that Zn ions are redox inert in biology, they have profound effects on redox metabolism. Thus, both Zn deficiency and Zn overload elicit oxidative stress that can lead to the death of nerve cells (Hao and Maret, 2006). The thyroid requires the presence of some essential elements other than 1 for the synthesis of thyroid hormones, for example Fe, Zn and Se (Zimmermann and Kohrle, 2002). Thyroid hormones exert their effects through nuclear receptors, and the T3 nuclear receptor is a Zn-containing protein (Miyamoto, 1991). 

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