Thyroid hormones tissue response

The thyroid hormones are responsible for optimal growth, development, function, and maintenance of all body tissues. Excess or inadequate amounts result in the signs and symptoms of hyperthyroidism or hypothyroidism, respectively (Table 38-4). Since T3 and T4 are qualitatively similar, they may be considered as one hormone in the discussion that follows. 

Another hormonal interrelationship exists between epinephrine and thyroid hormone. Tissues of rats treated with propylthiouracyl released very little fatty acids and did not respond to the addition of epinephrine. Conversely, in tissues of rats treated with triiodothyronine both basal release and response to epinephrine were exaggerated (Debons and Schwartz 1961 Deykin and Vaughan 1963). Release of free fatty acids by adipose tissue from rats treated with triiodothyronine or propylthiouracyl showed that the greater accumulation of fatty acids in the medium of tissues from triiodothyronine treated rats was at the expense of preformed tissue free fatty acids. The rates of both lipolysis and esterification were greater in these tissues so that no net change in total free fatty acids took place. However, the lipolytic system in tissues treated with triiodothyronine showed greater than normal response to epinephrine. 

Among vertebrate species, the neuro-endocrine-immime system is responsible for many complex, inter-related physiological processes including neuronal, homeostatic, reproductive and immune functions. There are four main types of hormone polypeptides, eicosanoids, steroids and thyroid hormones. Reflecting the inter-dependency of the neiiro-endocrine and immune systems, hormones, neuropeptides and other neiirotransmitters are known to be produced by some immune cells and play a role in the regulation of the immune system, while endocrine and nervous tissues express receptors for many substances produced by the immune system. The major focus of interest in endocrine disruption has... 

In permissiveness, one hormone enhances the responsiveness of the target tissue to a second hormone in other words, the first hormone increases the activity of the second. For example, the normal maturation of the reproductive system requires reproductive hormones from the hypothalamus, pituitary, and gonads as well as the presence of thyroid hormone. Although thyroid hormone by itself has no effect on the reproductive system, if it is absent the development of this system is delayed. Therefore, thyroid hormone is considered to have a permissive effect on the reproductive hormones, facilitating their actions causing sexual maturation. 

Current information indicates that OATP-E [30] is ubiquitously expressed in tissues [30, 37]. Some substrates transported by OATP-E include estrone-sulfate [30], prostaglandin E2 [30] and taurocholate [37]. The capacity for T3 and T4 transport and the wide tissue distribution suggests that OATP-E is largely responsible for the peripheral uptake of thyroid hormone [37]. Further studies are required to assess whether OATP-E is an important determinant of drag distribution. 

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. 

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. 

Large numbers of thyroid hormone receptors are found in the most hormone-responsive tissues (pituitary, liver, kidney, heart, skeletal muscle, lung, and intestine), while few receptor sites occur in hormone-unresponsive tissues (spleen, testes). The brain, which lacks an anabolic response to T3, contains an intermediate number of receptors. In congruence with their biologic potencies, the affinity of the receptor site forT4 is about ten times lower than that forT3. Under some conditions,... 

Reduction of thyroid activity and hormone effects can be accomplished by agents that interfere with the production of thyroid hormones, by agents that modify the tissue response to thyroid hormones, or by glandular destruction with radiation or surgery. Goitrogens are agents that suppress secretion of T3 and T4 to subnormal levels and thereby increase TSH, which in... 

I realize that this is a side track issue, but relevant all the same. Cycle protocols were an approach intended to facilitate optimal growth of muscle tissue. Remember there are two main muscle fiber types Type I, which is endurance orientated, and Type II which is strength orientated. Type "Ha", "Hb", and Type "He" are responsible for most musculature size and have the greatest potential for growth. Testosterone increases the number of Type II fibers at the expense of the Type I transformation. Growth hormone, Insulin, IGF-1, and thyroid hormones effect growth and hyperplasia of both fiber types. This should be another key relating to protocols that were utilized and why. 

Large numbers of thyroid hormone receptors are found in the most hormone-responsive tissues... 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Recently Izumo et al. [100] have reported that the myosin multichain family is composed of six different myosin heavy chains that are all responsive to thyroid hormones. The same myosin heavy chain gene can be regulated differently by thyroid hormones, even in opposite directions, depending on the tissue in which it is expressed. Differential expression and regulation by thyroid hormones have been demonstrated not only in heart muscle cells (atrium and ventricle) but also in several skeletal muscles (soleus, diaphragm, masseter, etc.). 

As with vitamin A, mast of the effects of vitamin D involve a nuclear receptor. The vitamin D receptor is a member of the steroid/thyroid hormone superfamily of receptors. When I a,2S-OHD binds to its receptor, the complex forms a hetcrodimer with an unoccupied RXR. This heterodimer subsequently binds to the regulatory regions on specific genes in target tissue. These regions are called vitamin D response elements (VDREs). The binding to VDREs can increase or decrease expression of genes. The proteins thus made carry out the functions of vitamin D. 

Observations from our laboratory show that post-infarcted myocardium is more tolerant to ischemia and reperfusion injury. Increased postischemic recovery of function and decreased LDH release were found in perfused rat hearts after 8 weeks of an acute myocardial infarction. This response was associated with downregulation of TRal and TRpi thyroid hormone nuclear receptors. Thus, it is likely that tissue hypothyroidism (at the receptor level) might account for the increased tolerance of those hearts to ischemia and reperfusion injury.215 See also chapter 2. 

Adams, B.A., D.G. Cyr and J.G. Eales. Thyroid hormone deiodination in tissues of American plaice, Hippoglossoides platessoides characterization and short-term responses to polychlorinated biphenyls (PCBs) 77 and 126. Comp. Biochem. Physiol. 127C 367-378, 2000. 

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