The Effect of Selenium on Changes in Thyroid Hormone-Related Deiodinase Enzyme Levels

Abstract

Purpose: The aim of this study is to investigate the effect of selenium on thyroid hormone-related deiodinase enzyme levels.
Materials and Methods: The experiments were carried out on adult male Wistar rats aged 2 months. In total, 32 rats were used in the study. The rats were divided into 4 groups; control (Control, n=8, saline was applied), hypothyroid (6-n-propyl thiouracil (Ptu), n=8, 1mg/kg/day Ptu), hypothyroid+sodium selenite (Sena, n=8, Ptu+0.5mg/kg/day sodium selenite) and hypothyroid+seleno-L- methionine (Semet, n=8, Ptu+0.7mg/kg/day seleno-L-methionine) group. All drugs were administered with gastric gavage technique for 21 days. After the experiment, the blood samples taken from the rats sacrificed in a heparin tube were centrifuged at 4000 rpm for 5 minutes and their plasmas were separated. The hippocampus of the decapitated rats was removed. Hippocampus (deiodinase 2) DIO2 and (deiodinase 3) DIO3 protein levels were measured with western blot method. Se values on plasma and hippocampus were measured with inductively coupled plasma-mass spectrometry. Plasma-free Triiodothyronine (T3) and thyroxine (T4) levels were measured using a commercial ELISA kit.
Results: Hippocampus DIO2 enzyme levels increased in the Ptu group compared to the control group (p=0.04) and DIO3 decreased (p=0.001). In the selenium (Se) supplemented groups, this difference in hypothyroidism disappeared.
Conclusion: These findings suggest that selenium supplementation may improve thyroid hormone levels in patients with hypothyroidism.

Keywords

• Deiodinase
• Hippocampus
• Thyroid Hormone
• Selenium

Tiroid Hormon İlişkili Deiyodinaz Enzim Seviyelerindeki Değişikliklere Selenyumun Etkisi

Abstract

Amaç: Bu çalışmanın amacı selenyumun tiroid hormon ilişkili deiodinaz enzim seviyeleri üzerine etkisini araştırmaktır.
Araçlar ve Yöntem: Deneyler 2 aylık, yetişkin, erkek Wistar Albino sıçanlar üzerinde gerçekleştirilmiştir. Çalışmada toplam 32 adet sıçan kullanılmıştır. Kontrol grubu (Kontrol, n=8, serum fizyolojik uygulanmıştır), hipotiroid (6-n-propil tiyourasil (Ptu), n=8, 1mg/kg/gün Ptu, hipotiroid+sodyum selenit (Sena, n=8, Ptu+0.5mg/kg/gün sodyum selenit) ve hipotiroid+seleno-L-metiyonin (Semet, n=8, Ptu+0.7mg/kg/gün seleno-L-metiyonin) grubu olmak üzere 4 grup oluşturulmuştur. Tüm maddeler 21 gün boyunca gastrik gavaj tekniği ile uygulanmıştır. Deney sonrası sakrifiye edilen sıçanlardan heparinli tüp içine alınan kan örnekleri 4000 rpm’ de 5 dakika süre ile santrifüj edilerek plazmaları ayrılmıştır. Dekapite edilen sıçanların hipokampüsleri çıkarılmıştır. Hipokampüs deiyodinaz 2 (DİO2) ve deiyodinaz 3 (DİO3) protein seviyeleri western blot yöntemi ile ölçülmüştür. Plazma ve beyin selenyum değerleri, kütle spektrometre yöntemi ile ölçülmüştür. Plazma serbest Triiyodotironin (T3) ve Tiroksin (T4) seviyeleri ticari ELISA kiti kullanılarak ölçülmüştür.
Bulgular: Hipokampüs DİO2 enzim seviyeleri Ptu grubunda kontrol grubuna göre artmış (p=0.04), DİO3 ise azalmıştır (p=0.001). Selenyum takviyeli gruplarda ise hipotiroidide gelişen bu farklılık ortadan kalkmıştır.
Sonuç: Bu bulgular hipotiroidi hastalarında selenyum takviyesinin tiroid hormon seviyesindeki bozuklukları iyileştirebileceğini düşündürmektedir.

Keywords

• Deiyodinaz
• Hipokampüs
• Tiroid Hormonları
• Selenyum

References

1. 1. De Escobar GM, Obregón MJ, Del Rey FE. Role of thyroid hormone during early brain development. Eur. J. Endocrinol. 2004;151(3):U25-U37.
2. 2. Mendoza A, Hollenberg AN. New insights into thyroid hormone action. Pharmacol. Ther. 2017;173:135-145.
3. 3. Cheng S-Y, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr. Rev. 2010;31(2):139-170.
4. 4. Brent GA. Mechanisms of thyroid hormone action. J. Clin. Investig. 2012;122(9):3035-3043.
5. 5. Dasgupta S, Lonard DM, O'Malley BW. Nuclear receptor coactivators: master regulators of human health and disease. Annu Rev Med. 2014;65:279-292.
6. 6. Mottis A, Mouchiroud L, Auwerx J. Emerging roles of the corepressors NCoR1 and SMRT in homeostasis. Genes Dev. 2013;27(8):819-835.
7. 7. Gereben B, Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr. Rev. 2008;29(7):898-938.
8. 8. Dentice M, Salvatore D. Local impact of thyroid hormone inactivation: Deiodinases: the balance of thyroid hormone. J. Endocrinol. 2011;209(3):273.

9. 9. Bianco AC, Kim BW. Deiodinases: implications of the local control of thyroid hormone action. J. Clin. Investig. 2006;116(10):2571-2579.
10. 10. Salvatore D, Bartha T, Harney JW, Larsen PR. Molecular biological and biochemical characterization of the human type 2 selenodeiodinase. Endocrinology. 1996;137(8):3308-3315.
11. 11. Luongo C, Trivisano L, Alfano F, Salvatore D. Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease. Front Endocrinol. 2013;4:115.
12. 12. Wassen F. Iodothyronine Deiodinases: structure-function analysis and their role in the regulation of thyroid hormone levels. Netherlands, Erasmus University Rotterdam Press. 2005.
13. 13. Wang Y, Zhan X, Zhang X, Wu R, Yuan D. Comparison of different forms of dietary selenium supplementation on growth performance, meat quality, selenium deposition, and antioxidant property in broilers. Biol. Trace Elem. Res. 2011;143(1):261-273.
14. 14. Kryukov GV, Castellano S, Novoselov SV, et al. Characterization of mammalian selenoproteomes. Science. 2003;300(5624):1439-1443.
15. 15. Papp LV, Lu J, Holmgren A, Khanna KK. From selenium to selenoproteins: synthesis, identity, and their role in human health. Antioxid Redox Signal. 2007;9(7):775-806.
16. 16. Contempre B, Dumont JE, Denel J-F, Many M-C. Effects of selenium deficiency on thyroid necrosis, fibrosis and proliferation: a possible role in myxoedematous cretinism. Eur. J. Endocrinol. 1995;133(1):99-109.
17. 17. Babür E, Tan B, Yousef M, Cinbaş S, Süer C, Dursun N. Deficiency but Not Supplementation of Selenium Impairs the Hippocampal Long-Term Potentiation and Hippocampus-Dependent Learning. Biol. Trace Elem. Res. 2019;192(2):252-262.
18. 18. IBM Corp. IBM SPSS Statistics V16. Published online 2008.
19. 19. Abdi H, Amouzegar A, Azizi F. Antithyroid drugs. Iran. J. Pharm. Sci. 2019;18(1):1.
20. 20. Esposito D, Rotondi M, Accardo G, et al. Influence of short-term selenium supplementation on the natural course of Hashimoto’s thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial. J. Endocrinol. Invest. 2017;40(1):83-89.
21. 21. Burmeister LA, Pachucki J, St. Germain DL. Thyroid hormones inhibit type 2 iodothyronine deiodinase in the rat cerebral cortex by both pre-and posttranslational mechanisms. Endocrinology. 1997;138(12):5231-5237.
22. 22. Dentice M, Marsili A, Zavacki A, Larsen PR, Salvatore D. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta Gen Subj. 2013;1830 (7):3937-3945.
23. 23. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002;23(1):38-89.
24. 24. Shen L, Van Dyck K, Luten J, Deelstra H. Diffusibility of selenate, selenite, seleno-methionine, and seleno-cystine during simulated gastrointestinal digestion. Biol. Trace Elem. Res. 1997;58(1):55-63.
25. 25. Burk RF, Norsworthy BK, Hill KE, Motley AK, Byrne DW. Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev. 2006;15(4):804-810.