Skip to main content
Springer Nature Link
Log in

Catechin induced modulation in the activities of thyroid hormone synthesizing enzymes leading to hypothyroidism

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Catechins, the flavonoids found in abundance in green tea, have many beneficial health effects such as antioxidative, anticarcinogenic, anti-inflammatory, antiallergic, and hypotensive properties. However, flavonoids have antithyroid/goitrogenic effect, although less information is available about the effect of pure catechin on thyroid physiology. The present investigation has been undertaken to explore the effect of catechin administration on thyroid physiology in rat model. For the in vivo experiment catechin was injected intraperitoneally (i.p.) at doses of 10, 20 and 30 mg/kg body to male albino rats for 15 and 30 days, respectively, and thyroid activities were evaluated with respect to determination of serum levels of thyroid hormones, thyroid peroxidase, 5′-deiodinase I (5′-DI), and Na+, K+-ATPase activities that are involved in the synthesis of thyroid hormone. Catechin decreased the activities of thyroid peroxidase and thyroidal 5′-deiodinase I, while Na+, K+-ATPase activity significantly increased in dose-dependent manner; substantial decrease in serum T3 and T4 levels coupled with significant elevation of serum TSH were also noted. Histological examinations of the thyroid gland revealed marked hypertrophy and/or hyperplasia of the thyroid follicles with depleted colloid content. In in vitro study, short-term exposure of rat thyroid tissue to catechin at the concentrations of 0.10, 0.20, and 0.30 mg/ml leads to decrease in the activities of thyroid peroxidase and 5′-deiodinase I, while the activity of thyroidal Na+, K+-ATPase remains unaltered even at high concentration of catechin treatment. The present study reinforces the concept that catechin, tea flavonoids possess potent antithyroid activity as evidenced from in vivo and in vitro studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Plate 1
Plate 2
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

ANOVA:

Analysis of variance

BSA:

Bovine serum albumin

BTE:

Black tea extract

COMT:

Catechol-O-methyltransferase

DIT:

Diiodotyrosine

DMSO:

Dimethylsulfoxide

DTE:

Dithioerythritol

EC:

(−)-Epicatechin

ECG:

(−)-Epicatechin gallate

EDTA:

Ethylenediamine tetraacetic acid

EGC:

(−)Epigallocatechin

EGCG:

(−)-Epigallocatechin gallate

ELISA:

Enzyme-linked immuno sorbent assay

GTC:

Green tea catechins

GTE:

Green tea extract

GTP:

Green tea polyphenols

H&E:

Hematoxylin & Eosin

H2O2 :

Hydrogen peroxide

MIT:

Monoiodotyrosine

MTT:

3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltrazolium bromide

Na+, K+-ATPase:

Sodium, Potassium Adenosine Triphosphatase

Na2ATP:

Adenosine-5′-triphosphoräure Dinatriumsalz

NIDDK:

National Institute of Diabetes and Digestive and Kidney Diseases

NIS:

Sodium-Iodide Symporter

PTU:

Propylthiouracil

RIA:

Radioimmunoassay

rT3:

Reverse T3

SDS:

Sodium dodecyl sulfate

T3:

Tri-iodothyronine

T4:

Thyroxin

TBG:

Thyroxine-binding globulin

TPO:

Thyroid peroxidase

TRH:

Thyrotropin-releasing Hormone

Tris-ATP:

Hydroxymethyl Aminomethane Hydrochloride Adenosine Triphosphate

TSH:

Thyroid stimulating hormone

5′-DI:

5′-Monodeiodinase-I

References

  1. Katiyar SK, Mukhtar H (1996) Tea in chemoprevention of cancer: epidemiologic and experimental studies (review). Int J Oncol 8:221–238

    PubMed  CAS  Google Scholar 

  2. Graham HN (1992) Green tea compostion, consumption, and ployphenol chemistry. Prev Med 21:334–350

    Article  PubMed  CAS  Google Scholar 

  3. Molinari M, Watt KD, Kruszyna T (2006) Acute liver failure induced by green tea extracts: case report and review of the literature. Liver Transpl 12:1892–1895

    Article  PubMed  Google Scholar 

  4. Chow HH, Cai Y, Hakim IA, Crowell JA, Shahi F, Brooks CA, Dorr RT, Hara Y, Alberts DS (2003) Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res 9:3312–3319

    PubMed  CAS  Google Scholar 

  5. Chengelis CP, Kirkpatrick JB, Regan KS, Radovsky AE, Beck MJ, Morita O, Tamaki Y, Suzuki H (2008) 28-Day oral (gavage) toxicity studies of green tea catechins prepared for beverages in rats. Food Chem Toxicol 46:978–989

    Article  PubMed  CAS  Google Scholar 

  6. Chacko SM, Thambi PT, Kuttan R, Nishigaki I (2010) Beneficial effects of green tea: a literature review. Chin Med 5:13–21

    Article  PubMed  Google Scholar 

  7. Wang CC, Chu KO, Chong WS, Li WY, Pang CP, Shum AS, Lau TK, Rogers MS (2007) Tea epigallocatechin-3-gallate increases 8-isoprostane level and induces caudal regression in developing rat embryos. Free Radic Biol Med 43:519–527

    Article  PubMed  CAS  Google Scholar 

  8. Imai T, Takami S, Hasumura M, Cho Y-M, Onose J, Hirose M (2008) Evaluation of toxicity of green tea catechins with 90-day dietary administration to F344 rats. Food Chem Toxicol 46:2224–2229

    Article  PubMed  Google Scholar 

  9. Lindsay RH, Gaitan E, Cooksey R (1989) Pharmacokinetics and intra-thyroidal effects of flavonoids. In: Gaitan E (ed) Environmental goitrogenesis. CRC Press, Bocu. Roton. FL, pp 43–56

    Google Scholar 

  10. Gaitan E, Cooksey RC, Lagan J, Lindsay RH (1995) Antithyroid effects in vivo and in vitro of vitexin: a C-glycosylflavone in millet. J Clin Endocrinol Metab 80:1144–1147

    Article  PubMed  CAS  Google Scholar 

  11. Chandra AK, Mukhopadhyay S, Ghosh D, Tripathy S (2006) Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats. Ind J Exp Biol 44:653–661

    CAS  Google Scholar 

  12. Ferreira ACF, Rosenthal D, Carvalho DP (2000) Thyroid peroxidase inhibition by Kalanchoe brasiliensis aqueous extract. Food Chem Toxicol 38:417–421

    Article  PubMed  CAS  Google Scholar 

  13. van der Schroder-Elst JP, van der Heide D, Kohrle J (1991) In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats. Am J Physiol 261:E227–E232

    Google Scholar 

  14. Koehrle J (2000) Flavonoids as a risk factor for goiter and hypothyroidism. In: Peter F, Wiersinga W, Hostalek U (eds) The Thyroid and Environment. Schattauer, Stuttgart, pp 41–63

    Google Scholar 

  15. Sakamoto Y, Mikuriya H, Tayama K, Takahashi H, Nagasawa A, Yano N, Yuzawa K, Ogata A, Aoki N (2001) Goitrogenic effects of green tea extract catechins by dietary administration in rats. Arch Toxicol 75:591–596

    Article  PubMed  CAS  Google Scholar 

  16. Satoh K, Sakamoto Y, Ogata A, Nagai F, Mikuriya H, Numazawa M, Tayama K, Aoki N (2002) Inhibition of aromatase activity by green tea extract catechins and their endocrinological effects of oral administration in rats. Food Chem Toxicol 40:925–933

    Article  PubMed  CAS  Google Scholar 

  17. Chandra AK, De N, Roy Choudhury S (2010b) Effect of different doses of un-fractionated green & black tea extracts on thyroid physiology. Human Exp Toxicol 30:884–896

    Google Scholar 

  18. Alexander NM (1962) A spectrophotometer assay of iodine oxidation by thyroid peroxidase. Anal Biochem 4:341

    Article  PubMed  CAS  Google Scholar 

  19. Esmann M (1988) ATPase and phosphate activity of Na+, K+-ATPase: molar and specific activity, protein determination. Methods Enzymol 156:105–115

    Article  PubMed  CAS  Google Scholar 

  20. Baginski ES, Foa PP, Zak B (1967) Determination of phosphate: study of labile organic phosphate interference. Clin Chim Acta 15:155–158

    Article  CAS  Google Scholar 

  21. Ködding R, Fuhrmann H, von zur Mühlen A (1986) Investigations on Iodothyronine deiodinase activity in the maturing rat brain. Endocrinology 118:1347–1352

    Article  PubMed  Google Scholar 

  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement from phenol reagent. J Biol Chem 193:265–270

    PubMed  CAS  Google Scholar 

  23. Greenwood FC, Hunter WM, Glover JS (1963) The preparation of 131I-labelled human growth hormone of high specific activity. Biochem J 89:114–123

    PubMed  CAS  Google Scholar 

  24. Corvilain B, Collyn L, van Sande J, Dumont JE (2000) Stimulation by iodide of H2O2 generation in thyroid slices from several species. American J Physiol Endocrinol and Metab 278:E692–E699

    CAS  Google Scholar 

  25. Roger P, Taton M, Van Sande J, Dumont JE (1988) Mitogenic effects of thyrotropin and adenosine 30,50- monophosphate in differentiated normal human thyroid cells in vitro. J Clinical Endocrinol Metab 66:1158–1165

    Article  CAS  Google Scholar 

  26. Gaitan E, Cooksey RC, Matthews D, Presson R (1983) In vitro measurement of anti-thyroid compounds and environmental goitrogens. J Clin Endocrinol Metab 56:767–773

    Article  PubMed  CAS  Google Scholar 

  27. Biswas SK, Sodhi A, Paul S (2001) Regulation of nitric oxide production by murine peritoneal macrophages treated in vitro with chemokine monocyte chemoattractant protein 1. Nitric Oxide 5:566–591

    Article  PubMed  CAS  Google Scholar 

  28. Fisher RA, Yates R (1974) Statistical Tables for Biological. Agricultural and Medical Research, Longman Group

    Google Scholar 

  29. Klaus S, Pültz S, Thöne-Reineke C, Wolfram S (2005) Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obes Relat Metab Disord 29:615–623

    Article  CAS  Google Scholar 

  30. Murase T, Nagasawa A, Suzuki J, Hase T, Tokimitsu I (2002) Beneficial effects of tea catechins on diet-induced obesity: stimulation of lipid catabolism in the liver. Int J Obesity 26:1459–1464

    Article  CAS  Google Scholar 

  31. Nagao T, Hase T, Tokimitsu I (2007) A green tea extract high in catechins reduces body fat and cardiovascular risks in humans. Obesity 15:1473–1483

    Article  PubMed  CAS  Google Scholar 

  32. Kao Y, Hiipakka RA, Liao S (2000) Modulation of obesity by green tea catechins. Am J Clin Nutr 72:1232–1233

    PubMed  CAS  Google Scholar 

  33. Ishihara K, Ito Y, Ichikawa T, Morohoshi Y, Nakamura T, Saegusa Y (2008) Effect of tea catechins on body fat accumulation in rats fed a normal diet. Biomed Res 29:27–32

    Article  PubMed  Google Scholar 

  34. Divi RL, Doerge DR (1996) Inhibition of thyroid peroxidase by dietary flavonoids. Chem Res Toxicol 9:16–23

    Article  PubMed  CAS  Google Scholar 

  35. Divi RL, Chang HC, Doerge DR (1997) Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanism of action. Biochem Pharmacol 54:1087–1096

    Article  PubMed  CAS  Google Scholar 

  36. Chandra AK, De N (2010) Goitrogenic/antithyroidal potential of green tea extract in relation to catechin in rats. Food Chem Toxicol 48:2304–2311

    Article  PubMed  CAS  Google Scholar 

  37. Köhrle J (1999) Local activation and inactivation of thyroid hormones: the deiodinase family. Mol Cell Endocrinol 151:103–119

    Article  PubMed  Google Scholar 

  38. Ferreira AC, Lisboa PC, Oliveira KJ, Lima LP, Barros IA, Carvalho DP (2002) Inhibition of thyroid type 1 deiodinase activity by flavonoids. Food Chem Toxicol 40:913–917

    Article  PubMed  CAS  Google Scholar 

  39. Spitzweg C, Morris JC (2002) Sodium Iodide Symporter (NIS) and Thyroid. Hormones 1:22–34

    PubMed  Google Scholar 

  40. Chow SY, Kemp JW, Woodbury DM (1982) Correlation of iodide transport with Na+, K+-ATPase, HCO3 “-ATPase and carbonic anhydrase activities in different functional states of the rat thyroid gland. J Endocrinol 92:371–379

    Article  PubMed  CAS  Google Scholar 

  41. Kundu S, Pramanik M, Roy S, De J, Biswas A, Ray AK (2006) Maintenance of brain thyroid hormone level during peripheral hypothyroid condition in adult rat. Life Sci 79:1450–1455

    Article  PubMed  CAS  Google Scholar 

  42. Pressley TA, Higham SC, Joson LA, Mercer DW (1995) Stimulation of Na+, K+ ATPase by thyrotropin in cultured thyroid follicular cells. Am J Physiol Cell Physiol 268:1252–1258

    Google Scholar 

  43. Le Grow AB, Fielding DC, Pressley TA (1999) Stimulation of Na+, K+-ATPase by hypothyroidism in the thyroid gland. J Endocrinol 160:453–460

    Article  Google Scholar 

  44. Do¨hler KD, Wong CC, von zur Mu¨hlen A (1979) The rat as model for the study of drug effects on thyroid function: consideration of methodological problems. Pharmacol Ther 5:305–318

    Article  Google Scholar 

  45. Capen CC (1995) Toxic response of the endocrine system. In: Klaassen CD, Amudr MO, Doull J (eds) Casarett and Doull’s toxicology: the basic science of poisons. Barnes and Noble, McGraw-Hill, New York, pp 617–640

Download references

Acknowledgments

Acknowledgement is due to the National Tea Research Foundation (NTRF), Kolkata, India, for providing fellowship to Neela De for this work. The authors are grateful to Prof. Arun K. Ray (Bose Institute, India) for his contribution in conducting enzyme study. The authors thank Dr Syed N Kabir, Scientist, Cell Biology & Physiology Division, Indian Institute of Chemical Biology (IICB), Kolkata, India, for his help in conducting RIA of TSH.

Author information

Authors and Affiliations

  1. Endocrinology & Reproductive Physiology Laboratory, Department of Physiology, University of Calcutta, Kolkata, West Bengal, India

    Amar K. Chandra & Neela De

  2. University College of Science & Technology, 92, Acharya Prafulla Chandra Road, Kolkata, 700 009, West Bengal, India

    Amar K. Chandra

Authors
  1. Amar K. Chandra
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Neela De
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Amar K. Chandra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chandra, A.K., De, N. Catechin induced modulation in the activities of thyroid hormone synthesizing enzymes leading to hypothyroidism. Mol Cell Biochem 374, 37–48 (2013). https://doi.org/10.1007/s11010-012-1503-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-012-1503-8

Keywords