Skeletal muscle thyroid hormones

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,... 

There is no such clear cut difTcrcnlialiun as metamorphosis in the mammal, but development is an extremely complex process and has been shown to depend upon the presence of adequate amounts of thyroid hormones. Deficient development, especially of the central nervous system, is marked in ehildren suffering from thyroid deficiency early in life, ansi this inadequacy cannot be overcome completely by medication commenced after the first few weeks. In the adult, thyroxine is important in the maintenance of energy turnover in most of the tissues of the body, such as the heart, skeletal muscle, liver, and kidney, Other physiological functions, most notably brain aclivity and reproduction, are also dependent upon thyroxine, although the metabolic rales of the tissues concerned in these functions do not seem to be altered. 

Recently Exton and co-workers [93] have proposed that adrenergic responsiveness in skeletal muscle is regulated by thyroid hormones at two levels, i.e., 1) stimulation of /3-adrenergic receptors and adenylate cyclase activity and 2) increased activity of phosphoprotein phosphatases. Such results would explain the effect of thyroid hormones on glycogen metabolism in muscle although the primary mechanism of these actions remains unknown. 

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.). 

Thiamine absorption occurs primarily in the proximal small intestine by both a saturable (thiamine transporter) process at low concentration (Ipmol/L, or lower) and by simple passive diffusion beyond that, though percentage absorption diminishes with increased dose. The absorbed thiamine undergoes intracellular phosphorylation, mainly to the pyrophosphate, but at the serosal side 90% of the transferred thiamine is in the firee form. Thiamine uptake is enhanced by thiamine deficiency and reduced by thyroid hormone, diabetes, and ethanol ingestion. The gene for the specific thiamine transporter has been identified, and the transporter cloned. Thiamine is carried by the portal blood to the liver. The firee vitamin occurs in the plasma, but the coenzyme, TPP, is the primary cellular component. Approximately 30 mg is stored in the body with 80% as the pyrophosphate, 10% as triphosphate, and the rest as thiamine and its monophosphate. About half of the body stores are found in skeletal muscles, with much of the remainder in heart, liver, kidneys, and nervous tissues (including the brain, which contains most of the triphosphate). 

Cortisol inhibits glucose utilization in peripheral tissues, such as skeletal muscle, adipose tissue, bone matrix, lymphoid tissue, and skin, by inhibiting glycolysis and promoting the use of fatty acids. This action is modulated by insulin and thyroid hormones but is potentiated by GH. 

IDL) to LDL, and probably also by maintaining lipoprotein lipase activity which promotes triglyceride clearance. In liver, kidney, skeletal muscle, cardiac muscle, and adipose tissue, thyroid hormone stimulates Na", K+-ATPase gene expression and promotes thermogenesis. 

Van der Linden, C.G., Muller, A. and Van Hardeveld, C. (2001) Mechanism of thyroid-hormone regulated expression of the SERCA genes in skeletal muscle implications for thermogenesis. Bioscience Reports, 21, 139—154. 

In vivo, deiodination is thought to be due to enzymes, deiodases. Indeed, due to a structural analogy with thyroid hormones, molecules labeled with Bolton-Hunter reagent or iodinated on a tyrosine moiety are recognized and quickly metabolized. Three classes of deiodases are known. Type I enzymes are mainly located in the liver, kidneys, and skeletal muscle, and deiodinate in the 5 and 5 positions of the tyrosine ring. Type II enzymes, in the brain, pituitary tissue and brown fat, and type III, localized in the central nervous system, both catalyze deiodination on the tyrosine 5 position. 

Cheema LR, Matty AJ (1978) Increased uptake of L-leucine C in the skeletal muscle of rainbow trout, Salmo gairdneri, after administration of growth hormone. Pak J Zoology 10 119-123 Cook RF, Eales JG (1987) Effects of feeding and photocycle on diel changes in plasma thyroid hormone levels in rainbow trout, Salmo gairdneri. J Exp Zool 242 161-169 Dabrowski KR (1986) Ontogenetic aspects of nutritional requirements in fish. Comp Biochem Physiol 85A 639-655... 

Endogenous TAs act as agonists of a TA-associated receptor 1 (TAARl) [12-14]. Thyronamines like 3-iodothyronamine, which are thyroid hormone derivatives, also show potent agonistic activity for TAARl [12]. TAARl mRNA is expressed in trace (in cerebellum, dorsal root ganglia, hippocampus, hypothalamus, liver, medulla, pancreas, pituitary, pontine reticular formation, prostate, skeletal muscle, and spleen), low (amygdala, kidney, lung, and small intestine), and moderate (stomach) amounts in human tissues [13]. 

Effects of ID in adult rats Feeding adult rats a diet with a low iodine content (LID) (0.02-0.06 pg I / g) results in undetectable circulating T4 levels, increased TSH and unaltered T3 concentrations, the same changes described for inhabitants of areas with severe ID. T4 decreases in all tissues studied so far (liver, brain, heart, and skeletal muscle) to the same degree as in plasma In contrast, T3 does not remain normal in tissues, as it does in plasma. T3 levels decrease, although not as markedly as T4 T3 in nuclei from liver and brain decrease 2- 2.5-fold with respect to nuclear T3 in rats on the I-supplemented LID (LID+I) All biological end-points of thyroid hormone action... 

Thyroid hormone Liver, kidney, skeletal muscle, heart, skin... 

The activity of the Na+-K+ pump has been proposed to be regulated by thyroid hormones and to account for a large contribution of the increased energy expenditure in hyperthyroidism. Microcalorimetry was used to measure erythrocyte [64] and lymphocyte [62 heat production rate during ouabain-induced inhibition of ATPasc, thus estimating the importance of the sodium-potassium pump in hyperthyroidism. The results of these studies show that the raised heat production rate in this condition was not due to increased energy expenditure by the pump. This was confirmed in microcalorimetric studies with mammalian. skeletal muscle [65,66] and hcpatocytes [66,67J. 

Administration of thyroid hormone to hypothyroid, thyroidectomized rats was found to increase heat production in liver, heart, kidney tissue as well as in skeletal muscle [66]. 

In a group of haemodialysis patients, muscle thermogenesis was evaluated by measurement of heat production in skeletal muscle samples [112]. Biopsies were taken from the vastus lateralis muscle by needle technique, using the same amount of muscle for each patient, about 45 mg. Microcalorimetric measurements were made in a perfusion calorimeter of the thermopile heat conduction type, as previously described. Blood samples for measurement of thyroid hormone concentration were collected the morning before dialysis after the patients had been fasting for 12 h. About 40% of the group of haemodialysis patient were found to have decreased muscle heat production... 

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