Metabolism thyroid hormones affecting

Thyroid hormones affect a wide variety of peripheral tissues throughout the individual s life.8,55 In some situations, these hormones exert a direct effect on cellular function (e.g., T4 and T3 appear to increase cellular metabolism by directly increasing oxidative enzyme activity). In other instances, thyroid hormones appear to play a permissive role in facilitating the function of other hormones. For instance, thyroid hormones must be present for growth hormone to function properly. The principal effects of the thyroid hormones are listed below. 

Metabolic Effects. Thyroid hormones affect energy substrate utilization in a number of ways. For instance, these hormones increase intestinal glucose absorption and increase the activity of several enzymes involved in carbohydrate metabolism. Thyroid hormones enhance lipolysis by increasing the response of fat cells to other lipolytic hormones. In general, these and other metabolic effects help to increase the availability of glucose and lipids for increased cellular activity. 

The thyroid hormones affect mahy facets of metabolism [25-32]. The metabolism of nitrogen, carbohydrates, and lipids are all markedly altered in hyper-and hypothyroidism. The biochemical sequence leading to the alteration is not known, yet these metabolic changes are of considerable importance in clinical medicine. 

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). 

By selectively affecting gene transcription and the consequent production of appropriate target mRNAs, the amounts of specific proteins are changed and metabolic processes are influenced. The influence of each of these hormones is quite specific generally, the hormone affects less than 1% of the genes, mRNA, or proteins in a target cell sometimes only a few are affected. The nuclear actions of steroid, thyroid, and retinoid hormones are quite well defined. Most evidence sug-... 

Drugs can affect thyroid function in a number of ways.41 Effects of drugs on thyroid hormone protein binding, LT4 absorption, and metabolism have been discussed previously. Several commonly used medications can alter thyroid hormone secretion. 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Thyroid disorders encompass a variety of disease states affecting thyroid hormone production or secretion that result in alterations in metabolic stability. Hyperthyroidism and hypothyroidism are the clinical and biochemical syndromes resulting from increased and decreased thyroid hormone production, respectively. 

By definition all hormones affect the behavior of their target cells. Examples of the interplay between endocrine disturbances and their biochemical consequences are provided by some of the diseases of the thyroid, which directly affects basal metabolic rate, and diabetes mellitus, where glucose metabolism is deranged. 

Demonstration that the effects of thyrotoxicosis or goiter are due to an excess or deficiency in (thyroxine + T3) secretion does not explain how the diseases originate nor why development and metabolic rate are affected. It is thought that some cases of thyrotoxicosis (Graves disease) may be caused by abnormal immune responses mimicking the effects of thyroid-stimulating hormone on the thyroid gland. 

There is no discrete target tissue for thyroid hormones virtually every cell in the body is affected by thyroid hormones in some way. These hormones are intimately involved in the maintenance of normal function in virtually every cell type, including cellular responsiveness to other hormones, to the availability of metabolic substrates, to growth factors, and so on. Thyroid dysfunction can produce dramatic changes in the metabolism of proteins, carbohydrates, and lipids at the cellular level that can have repercussions for the operation of the cardiovascular, gastrointestinal, musculoskeletal, reproductive, and nervous systems. Some of the clinical manifestations of thyroid dysfunction are presented next in the discussions of hypothyroid and hyperthyroid states. 

Hypothyroidism developed within 2 weeks of rifampicin therapy in these patients and resolved when it was withdrawn. Rifampicin increases thyroxine clearance, possibly by enhancing hepatic thyroxine metabolism and the biliary excretion of iodothyronine conjugates. In healthy volunteers rifampicin reduces circulating thyroid hormone concentrations without affecting thyrotropin, suggesting that rifampicin directly reduces thyroid hormone concentrations. 

The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42 Agents That Affect Bone Mineral Homeostasis. 

The concept that plasma membrane transport plays a key role in the regulation of intracellular thyroid hormone levels is supported by studies with a monoclonal antibody against an antigen exposed on rat liver cells [107], This antibody inhibited the uptake of different iodothyronines by rat hepatocytes under initial rate conditions as well as the metabolism of these compounds during prolonged incubations [107]. Uptake and metabolism of T4, T3 and rT3 were affected to the same extent, suggesting that a single system operates in the transport of different iodothyronines, which is opposite to the view advanced above. However, it is not excluded that the antibody interacts with a component of the plasma membrane and thereby affects multiple transport systems. 

Insulin and thyroid hormones positively affect hepatic LDL-receptor interactions therefore, the hypercholesterolaemia and increased risk of atherosclerosis associated with uncontrolled diabetes or hypothyroidism is likely due to decreased hepatic LDL uptake and metabolism. 

Other endocrine sy.stems are interrelated. Both cortico.stc-roids and thyroid hormones may increase the requirement for pyridoxine and affect pyridoxal S-phosphate-dependent metabolic processes. Moreover, there appear to be associations between vitamin B<, and anterior pituitary hormones that seem to involve the hypothalamus, S-hydroxytryptamine, and dopamine. The latter two neurolransmitters are synthesized by metabolic proce.sse that require pyridoxal S-phu.sphate. 

The exact mechanism of action is not well understood. Thyroid hormones are needed for metabolism, growth, and development. Most organ systems are affected by thyroid hormones. Thyroid hormones cause an increase in the basal metabolic rate, in oxygen consumption, and in the metabolism of... 

Protirelin (thyrotrophin-releasing hormone. TRH. thyrotrophin-releasing hormone factor. TRF) is a tripeptide agent that modulates the release of thyrotrophin (and prolactin) from the pituitary and thence, in turn, thyroid hormone that affects metabolism and a number of other processes in the body. Therapeutically, protirelin is used to assess thyroid disorders and function in patients who suffer from hypopituitarism or hyperthyroidism. 

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