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Wednesday, 11 December 2013

The Effects of Thyroid hormone (2)

 Thyroid hormone (triiodothyronine (T3) and thyroxine (T4)), produced by the thyroid gland, plays an important role in regulation of metabolism, including directly boosts energy metabolism and triggers rapid protein synthesis and regulates mitochondrial gene transcription, etc. Iodine is necessary for the production of T3 and T4, deficiency of Iodine can lead to enlarge thyroid grand and goitre.
11. Thyroid hormone stimulates protein synthesis
According to the study by North Shore-Long Island Jewish Health System, Thyroid hormones affect cardiac growth and phenotype; however, the mechanisms by which the hormones induce cardiomyocyte hypertrophy remain uncharacterized. Tri-iodo-L-thyronine (T3) treatment of cultured cardiomyocytes for 24 h resulted in a 41 +/- 5% (p < 0.001) increase in [(3)H]leucine incorporation into total cellular protein. This response was abrogated by the phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. Co-immunoprecipitation studies showed a direct interaction of cytosol-localized thyroid hormone receptor TRalpha1 and the p85alpha subunit of PI3K. T3 treatment rapidly increased PI3K activity by 52 +/- 3% (p < 0.005)(11).  

12. Thyroid hormone and skeletal growth
Understanding how bone growth is regulated by hormonal and mechanical factors during early growth periods is important for optimizing the attainment of peak bone mass to prevent or postpone the occurrence of fragility fractures later in life. According to the study by Musculoskeletal Disease Center, Loma Linda VA HealthCare System , there is an important period prior to puberty when the effects of GH are surprisingly small and TH plays a critical role in the regulation of skeletal growth. Daily administration of T3/T4 during days 5 to 14, the time when serum levels of T3 increase rapidly in mice, rescued the skeletal deficit in TH-deficient mice but not in mice lacking both TH and GH. However, treatment of double-mutant mice with both GH and T3/T4 rescued the bone density deficit. Increased body fat in the TH-deficient as well as TH/GH double-mutant mice was rescued by T3/T4 treatment during days 5 to 14(12).

13. Triiodothyronine stimulates glucose transport in bone cells
In the study to evaluate whether 3,3',5-triiodo-l-thyronine (T₃) stimulates the uptake of glucose in osteoblastic cells, PyMS (a cell line derived from rat bone) cells were kept in serum-free culture medium and treated with T₃, found that T₃ did not influence the cell number but slightly (1.3-fold) increased the protein content of the cell cultures.  2DG ([1-¹⁴C]-2-deoxy-D: -glucose)uptake was low in serum-deprived cell cultures and was increased by T₃ (up to 2.5-fold at 1 nmol l⁻¹ after 4 days) in a dose- and time-dependent manner. Triiodothyronine at 1 nmol l⁻¹ increased GLUT1 and GLUT3 abundance in membranes. Therefore, increased glucose uptake induced by T₃ in osteoblasts may be mediated by the known high-affinity glucose transporters GLUT1 and GLUT3(13).

14. Thyronamines and body temperature and heart rate
 The thyronamines which are decarboxylated thyroid hormones initiating physiological actions like lowering body temperature and heart rate, thereby acting in opposite direction to the classical thyroid hormones. So far it is believed that thyronamines function via the activation of a G-protein coupled receptor, TAAR1. The objective of this review is to summarise the recent findings in thyroid hormone synthesis and action and to discuss their implications for diagnosis of thyroid disease and for treatment of patients, according to the study by Institute of Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin(14).

15. Effect of iodine deficiency and cold exposure on thyroxine 5'-deiodinase activity
In the study to measure the thyroxine 5'-deiodinase I (T(4)5'D-I) activity in thyroid, liver, and kidney and thyroxine 5'-deiodinase II (T(4)5'D-II) activity in brown adipose tissue (BAT) in rats on a low-iodine diet (LID)  and to test the possibility that increased deiodinase activity in these tissues might contribute to the maintenance of ther serum 3,5,3'-triiodothyronine (T3) level, found that  increased thyroxine (T4)-to-T3 conversion in the greatly enlarged thyroids of LID rats contributed to the maintenance of serum T3. T(4)5'D-II activity in BAT was markedly increased in LID rats and was further greatly increased on cold exposure(15).

16. Chemiluminescent and respiratory responses related to thyroid hormone-induced liver oxidative stress
In the study of Chemiluminescent and respiratory responses  in the liver of rats treated with 0.1 mg of triiodothyronine (T3)/kg for 1 to 7 days, showed that  the calorigenic response in the hyperthyroid state is accompanied by the development of an hepatic oxidative stress characterized by enhanced spontaneous chemiluminescence, enhanced NADPH-dependent microsomal respiration and a decreased antioxidant cellular activity(16).

17. Oxidative stress and thyroid hormones
The liver metabolizes the thyroid hormones and regulates their systemic endocrine effects so liver disease could affect thyroid hormone metabolism. In the study to investigate serum levels of oxidative stress and antioxidant in liver diseases as prognostic markers and know the importance of these antioxidants level in relation to thyroid hormones, researchers at the Ain Shams University, found that measurement of the total T(3), NO, MDA, GSH reduced and GSHPx as biomarkers for liver diseases might be a beneficial tool, helping in monitoring the state of liver disease patients.(17).

18. Radioiodine treatment and oxidative stress in thyroidectomised patients
Post-operative radioiodine treatment of differentiated thyroid cancer occupies a well determined place in the treatment policy of this disease. In the study to measure erythrocyte malondialdehyde (MDA) levels, as a marker of lipid peroxidation, erythrocyte reduced glutathione (GSH) levels and activities of GSH-Peroxidase and GSH-Reductase as antioxidants, showed that erythrocyte MDA levels were significantly higher, and erythrocyte GSH levels and activities of GSH-related enzymes were significantly lower in thyroidectomised patients after surgery than in healthy controls. Additionally, according to their thyroid hormone levels the patients had hypothyroidism at this time. In patients 2 days after radioiodine treatment both MDA and GSH levels and GSH-related enzyme activities were significantly increased when compared to their own initial levels(18).

19. Oxidant/antioxidant balance in patients with thyroid cancer
In the study to compare the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of lipid peroxidation product malondialdehyde (MDA) in blood samples of thyroid cancer patients compared to healthy controls, found that tThe superoxide dismutase does not seem to change with thyroid cancer and thyroidectomy but both antioxidant glutathione peroxidase and lipid peroxidation product malondialdehyde do. These preliminary findings may point out oxidant/antioxidant imbalance associated with thyroid cancer.(19).

20. Metabolic parameters and thyroid hormones and the level of gastric peptides in children with autoimmune thyroid diseases
Overweight and diseases connected with it are increasing problems in children and adults. In the sudy by Medical University of Białystok, to analyze the relationship between lipid-carbohydrate metabolism parameters and thyroid hormones and the level of gastric peptides (ghrelin and obestatin) in young patients with Graves' disease, Hashimoto's thyroiditis and in children with simple goiter, showed that the disturbances in carbohydrate parameters in thyroid diseases have an essential effect on change of hormone-controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in Subclinical hypothyroidism)(20).
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Sources

(11) http://www.ncbi.nlm.nih.gov/pubmed/16717100
(12) http://www.ncbi.nlm.nih.gov/pubmed/22513648
(13) http://www.ncbi.nlm.nih.gov/pubmed/22258767
(14) http://www.ncbi.nlm.nih.gov/pubmed/21835056
(15) http://www.ncbi.nlm.nih.gov/pubmed/1996620
(16) http://www.ncbi.nlm.nih.gov/pubmed/3215552
(17) http://www.ncbi.nlm.nih.gov/pubmed/19818291
(18) http://www.ncbi.nlm.nih.gov/pubmed/9774495
(19) http://www.ncbi.nlm.nih.gov/pubmed/19030755
(20) http://www.ncbi.nlm.nih.gov/pubmed/20583539