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DOI: 10.1055/a-0919-3879
Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A
Publikationsverlauf
received 11. Januar 2019
accepted 09. Mai 2019
Publikationsdatum:
07. Juni 2019 (online)
![](https://www.thieme-connect.de/media/hmr/201910/lookinside/thumbnails/2019-01-0012_10-1055-a-0919-3879-1.jpg)
Abstract
Plastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.
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References
- 1 Richter CA, Taylor JA, Ruhlen RR. et al. Estradiol and bisphenol A stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells. Environ Health Perspect 2007; 115: 902-908
- 2 Erkekoglu P, Zeybek ND, Giray B. et al. The effects of di(2-ethylhexyl)phthalate exposure and selenium nutrition on sertoli cell vimentin structure and germ-cell apoptosis in rat testis. Arch Environ Contam Toxicol 2012; 62: 539-547
- 3 Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res 2008; 108: 177-184
- 4 Kovacic P. How dangerous are phthalate plasticizers? Integrated approach to toxicity based on metabolism, electron transfer, reactive oxygen species and cell signaling. Med Hypotheses 2010; 74: 626-628
- 5 Dirtu AC, Geens T, Dirinck E. et al. Phthalate metabolites in obese individuals undergoing weight loss: Urinary levels and estimation of the phthalates daily intake. Environ Int 2013; 59: 344-353
- 6 Michałowicz J. Bisphenol A–sources, toxicity and biotransformation. Environ Toxicol Pharmacol 2014; 37: 738-758
- 7 Kappenstein O, Vieth B, Luch A. et al. Toxicologically relevant phthalates in food. Exp Suppl 2012; 101: 87-106
- 8 Saravanabhavan G, Murray J. Human biological monitoring of diisononyl phthalate and diisodecyl phthalate: A review. J Environ Public Health 2012; 810501
- 9 Kumar P. Role of Plastics on Human Health. Indian J Pediatr 2018; 85: 384-389
- 10 Meeker JD, Calafat AM, Hauser R. Di(2-ethylhexyl) phthalate metabolites may alter thyroid hormone levels in men. Environ Health Perspect 2007; 115: 1029-1034
- 11 Liu C, Zhao L, Wei L, Li L. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats. Environ Sci Pollut Res Int 2015; 22: 12711-12719
- 12 Huang PC, Tsai CH, Liang WY. et al. Early phthalates exposure in pregnant women is associated with alteration of thyroid hormones. PLoS One 2016; 11: e0159398
- 13 Wu Y, Beland FA, Fang JL. Effect of triclosan, triclocarban, 2,2',4,4'-tetrabromodiphenyl ether, and bisphenol A on the iodide uptake, thyroid peroxidase activity, and expression of genes involved in thyroid hormone synthesis. Toxicol In Vitro 2016; 32: 310-319
- 14 Silva MMD, Xavier LLF, Gonçalves CFL. et al. Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro. Endocr Connect 2018; Sep 1. pii: /journals/ec/aop/ec-18-0348.xml DOI: 10.1530/EC-18-0348. [Epub ahead of print]
- 15 Köhrle J. Selenium and the control of thyroid hormone metabolism. Thyroid 2005; 15: 841-853
- 16 Gereben B, Zavacki AM, Ribich S. et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev 2008; 29: 898-938
- 17 Dentice M, Marsili A, Zavacki A. et al. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta 2013; 1830: 3937-3945
- 18 Bianco AC, Salvatore D, Gereben B. et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev 2002; 23: 28-89
- 19 Bianco AC, Kim BW. Deiodinases: Implications of the local control of thyroid hormone action. J Clin Invest 2006; 116: 2571-2579
- 20 de Vries EM, van Beeren HC, Ackermans MT. et al. Differential effects of fasting vs. food restriction on liver thyroid hormone metabolism in male rats. J Endocrinol 2015; 224: 25-35
- 21 Olivares EL, Marassi MP, Fortunato RS. et al. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology 2007; 148: 4786-4792
- 22 Maia AL, Goemann IM, Meyer EL. et al. Deiodinases: The balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J Endocrinol 2011; 209: 283-297
- 23 Morse DC, Groen D, Veerman M. et al. Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats. Toxicol Appl Pharmacol 1993; 122: 27-33
- 24 Raasmaja A, Viluksela M, Rozman KK. Decreased liver type I 5'-deiodinase and increased brown adipose tissue type II 5'-deiodinase activity in 2,3,7,8-tetrachlorobibenzo-p-dioxin (TCDD)-treated Long-Evans rats. Toxicology 1996; 114: 199-205
- 25 Wade MG, Parent S, Finnson KW. et al. Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium. Toxicol Sci 2002; 67: 207-218
- 26 Schmutzler C, Gotthardt I, Hofmann PJ. et al. Endocrine disruptors and the thyroid gland--a combined in vitro and in vivo analysis of potential new biomarkers. Environ Health Perspect 2007; 115 (Suppl 1) 77-83
- 27 Lisbôa PC, Curty FH, Moreira RM. et al. Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland. Braz J Med Biol Res 1997; 30: 1479-1484
- 28 Lisbôa PC, Curty FH, Moreira RM. et al. Sex steroids modulate rat anterior pituitary and liver iodothyronine deiodinase activities. Horm Metab Res 2001; 33: 532-535
- 29 Bianco AC, Nunes MT, Hell NS. et al. The role of glucocorticoids in the stress-induced reduction of extrathyroidal 3,5,3'-triiodothyronine generation in rats. Endocrinology 1987; 120: 1033-1038
- 30 Louzada RA, Santos MC, Cavalcanti-de-Albuquerque JP. et al. Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure. Am J Physiol Endocrinol Metab 2014; 307: E1020-E1029
- 31 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254
- 32 Aloisi AM, Della Seta D, Ceccarelli I. et al. Bisphenol-A differently affects estrogen receptors-alpha in estrous-cycling and lactating female rats. Neurosci Lett 2001; 310: 49-52
- 33 Honma T, Miyagawa M, Suda M. et al. Effects of perinatal exposure to bisphenol A on brain neurotransmitters in female rat offspring. Ind Health 2006; 44: 510-524
- 34 Miao S, Gao Z, Kou Z. et al. Influence of bisphenol A on developing rat estrogen receptors and some cytokines in rats: A two-generational study. J Toxicol Environ Health A 2008; 71: 1000-1008
- 35 McCaffrey KA, Jones B, Mabrey N. et al. Sex specific impact of perinatal bisphenol A (BPA) exposure over a range of orally administered doses on rat hypothalamic sexual differentiation. Neurotoxicology 2013; 36: 55-62
- 36 Wang C, Niu R, Zhu Y. et al. Changes in memory and synaptic plasticity induced in male rats after maternal exposure to bisphenol A. Toxicology 2014; 322: 51-60
- 37 Moog NK, Entringer S, Heim C. et al. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience 2017; 342: 68-100
- 38 Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010; 316: 165-171
- 39 Vargas-Uricoechea H, Bonelo-Perdomo A. Thyroid dysfunction and heart failure: Mechanisms and associations. Curr Heart Fail Rep 2017; 14: 48-58
- 40 Bloise FF, Cordeiro A, Ortiga-Carvalho TM. Role of thyroid hormone in skeletal muscle physiology. J Endocrinol 2018; 236: R57-R68
- 41 Ribeiro E, Ladeira C, Viegas S. Occupational exposure to bisphenol A (BPA): A reality that still needs to be unveiled. Toxics 2017; 5 pii: E22
- 42 Geens T, Aerts D, Berthot C. et al. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol 2012; 50: 3725-3740
- 43 Gong Y, Tian H, Dong Y. et al. Thyroid disruption in male goldfish (Carassius auratus) exposed to leachate from a municipal waste treatment plant: Assessment combining chemical analysis and in vivo bioassay. Sci Total Environ 2016; 554-555 64–72
- 44 Schneider MJ, Fiering SN, Thai B. et al. Targeted disruption of the type 1 selenodeiodinase gene (Dio1) results in marked changes in thyroid hormone economy in mice. Endocrinology 2006; 147: 580-589
- 45 Visser WE, Bombardieri CR, Zevenbergen C. et al. Tissue-specific suppression of thyroid hormone signaling in various mouse models of aging. PLoS One 2016; 11: e0149941
- 46 Silvestri E, Lombardi A, de Lange P. et al. Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels. Am J Physiol Endocrinol Metab 2008; 294: E1160-E1168
- 47 da Costa VM, Moreira DG, Rosenthal D. Thyroid function and aging: Gender-related differences. J Endocrinol 2001; 171: 193-198
- 48 Correa da Costa VM, Rosenthal D. Effect of aging on thyroidal and pituitary T4-5'-deiodinase activity in female rats. Life Sci 1996; 59: 1515-1520
- 49 Donda A, Lemarchand-Béraud T. Aging alters the activity of 5'-deiodinase in the adenohypophysis, thyroid gland, and liver of the male rat. Endocrinology 1989; 124: 1305-1309
- 50 Meeker JD, Ferguson KK. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Environ Health Perspect 2011; 119: 1396-1402
- 51 Arnaldi LA, Borra RC, Maciel RM. et al. Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors. Thyroid 2005; 15: 210-221
- 52 Piekiełko-Witkowska A, Nauman A. Iodothyronine deiodinases and cancer. J Endocrinol Invest 2011; 34: 716-728
- 53 de Souza Meyer EL, Dora JM, Wagner MS. et al. Decreased type 1 iodothyronine deiodinase expression might be an early and discrete event in thyroid cell dedifferentation towards papillary carcinoma. Clin Endocrinol (Oxf) 2005; 62: 672-678
- 54 Wawrzynska L, Sakowicz A, Rudzinski P. et al. The conversion of thyroxine to triiodothyronine in the lung: comparison of activity of type I iodothyronine 5' deiodinase in lung cancer with peripheral lung tissues. Monaldi Arch Chest Dis 2003; 59: 140-145
- 55 Sabatino L, Iervasi G, Ferrazzi P. et al. A study of iodothyronine 5'-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues. Life Sci 2000; 68: 191-202
- 56 Pachucki J, Ambroziak M, Tanski Z. et al. Type I 5'-iodothyronine deiodinase activity and mRNA are remarkably reduced in renal clear cell carcinoma. J Endocrinol Invest 2001; 24: 253-261