Maturitas
Volume 55 , Pages S14-S25 , 1 November 2006

Effects of isoflavonoids and other plant-derived compounds on the hypothalamus–pituitary–thyroid hormone axis

  • Inka Hamann

      Affiliations

    • Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum, Charité, Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 30 450 576097; fax: +49 30 450 524922.
    • ,
  • D. Seidlova-Wuttke

      Affiliations

    • Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen, Germany
    • ,
  • W. Wuttke

      Affiliations

    • Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Str. 40, D-37075 Goettingen, Germany
    • ,
  • J. Köhrle

      Affiliations

    • Institut für Experimentelle Endokrinologie und Endokrinologisches Forschungszentrum, Charité, Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany

References 

  1. Köhrle J. The trace element selenium and the thyroid gland. Biochimie. 1999;81(5):527–533[review]
  2. Gillam MP, Sidhaye AR, Lee EJ, Rutishauser J, Stephan CW, Kopp P. Functional characterization of pendrin in a polarized cell system. Evidence for pendrin-mediated apical iodide efflux. J Biol Chem. 2004;279(13):13004–13010
  3. Yoshida A, Hisatome I, Taniguchi S, et al. Mechanism of iodide/chloride exchange by pendrin. Endocrinology. 2004;145(9):4301–4308
  4. Martin-Belmonte F, Alonso MA, Zhang X, Arvan P. Thyroglobulin is selected as luminal protein cargo for apical transport via detergent-resistant membranes in epithelial cells. J Biol Chem. 2000;275(52):41074–41081
  5. De Deken X, Wang D, Dumont JE, Miot F. Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system. Exp Cell Res. 2002;273(2):187–196
  6. Brix K, Linke M, Tepel C, Herzog V. Cysteine proteinases mediate extracellular prohormone processing in the thyroid. Biol Chem. 2001;382(5):717–725[review]
  7. Hamilton JA, Benson MD. Transthyretin: a review from a structural perspective. Cell Mol Life Sci. 2001;58(10):1491–1521[review]
  8. Palha JA. Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002;40(12):1292–1300[review]
  9. Buettner C, Grasberger H, Hermansdorfer K, Chen B, Treske B, Janssen OE. Characterization of the thyroxine-binding site of thyroxine-binding globulin by site-directed mutagenesis. Mol Endocrinol. 1999;13(11):1864–1872
  10. Schussler GC. The thyroxine-binding proteins. Thyroid. 2000;10(2):141–149[review]
  11. Friesema EC, Jansen J, Visser TJ. Thyroid hormone transporters. Biochem Soc Trans. 2005;33(Pt 1):228–232
  12. Tohyama K, Kusuhara H, Sugiyama Y. Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood–brain-barrier. Endocrinology. 2004;145(9):4384–4391
  13. Zhou Y, Samson M, Francon J, Blondeau JP. Thyroid hormone concentrative uptake in rat erythrocytes. Involvement of the tryptophan transport system T in countertransport of tri-iodothyronine and aromatic amino acids. Biochem J. 1992;281(Pt 1):81–86
  14. Yan Z, Hinkle PM. Saturable, stereospecific transport of 3,5,3′-triiodo-l-thyronine and l-thyroxine into GH4C1 pituitary cells. J Biol Chem. 1993;268(27):20179–20184
  15. 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[review]
  16. Köhrle J, Jakob F, Contempre B, Dumont JE. Selenium, the thyroid, and the endocrine system. Endocr Rev. 2005;26(7):944–984
  17. Köhrle J. Thyroid hormone metabolism and action. Z Arztl Fortbild Qualitatssich. 2004;98(Suppl. 5):17–24[review]
  18. Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21(2):113–131[review]
  19. Horn-Ross PL, Hoggatt KJ, Lee MM. Phytoestrogens and thyroid cancer risk: the San Francisco Bay Area thyroid cancer study. Cancer Epidemiol Biomarkers Prev. 2002;11(1):43–49
  20. Oak MH, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem. 2005;16(1):1–8
  21. Newbold RR, Banks EP, Bullock B, Jefferson WN. Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Res. 2001;61(11):4325–4328
  22. Izumi T, Piskula MK, Osawa S, et al. Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr. 2000;130(7):1695–1699
  23. Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG, Postellon DC. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. 1995;96(1 Pt 1):148–150[review]
  24. Winterhoff H, Gumbinger HG, Vahlensieck U, Kemper FH, Schmitz H, Behnke B. Endocrine effects of Lycopus europaeus L. following oral application. Arzneimittelforschung. 1994;44(1):41–45
  25. Vonhoff C, Baumgartner A, Hegger M, Korte B, Biller A, Winterhoff H. Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats. Life Sci. 2006;78(10):1063–1070
  26. Sourgens H, Winterhoff H, Gumbinger HG, Kemper FH. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med. 1982;45(2):78–86
  27. van Wyk JJ, Arnold MB, Wynn J, Pepper F. The effects of a soybean product on thyroid function in humans. Pediatrics. 1959;24:752–760
  28. Hydovitz JD. Occurrence of goiter in an infant on a soy diet. N Engl J Med. 1960;262:351–353
  29. Shepard TH, Pyne GE, Kirschvink JF, Mc Lean CM. Soybean goiter. N Engl J Med. 1960;262:1099–1103
  30. Ripp JA. Soybean-induced goiter. Am J Dis Child. 1961;102:106–109
  31. Kimura S, Suwa J, Ito M, Sato H. Development of malignant goiter by defatted soybean with iodine-free diet in rats. Gann. 1976;67(5):763–765
  32. Kay T, Kimura M, Nishing K, Itokawa Y. Soyabean, goitre, and prevention. J Trop Pediatr. 1988;34(3):110–113
  33. van der Heide D, Kastelijn J, Schröder-van der Elst JP. Flavonoids and thyroid disease. Biofactors. 2003;19(3/4):113–119[review]
  34. Watanabe S, Terashima K, Sato Y, Arai S, Eboshida A. Effects of isoflavone supplement on healthy women. Biofactors. 2000;12(1–4):233–241
  35. Duncan AM, Merz BE, Xu X, Nagel TC, Phipps WR, Kurzer MS. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab. 1999;84(1):192–197
  36. Duncan AM, Underhill KE, Xu X, Lavalleur J, Phipps WR, Kurzer MS. Modest hormonal effects of soy isoflavones in postmenopausal women. J Clin Endocrinol metab. 1999;84(10):3479–3484Erratum in: J Clin Endocrinol Metab 2000;85(1):448
  37. Ishizuki Y, Hirooka Y, Murata Y, Togashi K. The effects on the thyroid gland of soybeans administered experimentally in healthy subjects. Nippon Naibunpi Gakkai Zasshi. 1991;67(5):622–629
  38. Divi RL, Doerge DR. Inhibition of thyroid peroxidase by dietary flavonoids. Chem Res Toxicol. 1996;9(1):16–23
  39. Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997;54(10):1087–1096
  40. Chang HC, Doerge DR. Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Toxicol Appl Pharmacol. 2000;168(3):244–252
  41. Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002;110(Suppl 3):349–353[review]
  42. Schröder-van der Elst JP, Smit JW, Romijn HA, van der Heide D. Dietary flavonoids and iodine metabolism. Biofactors. 2003;19(3/4):171–176
  43. Ferreira AC, Lisboa PC, Oliveira KJ, Lima LP, Barros IA, Carvalho DP. Inhibition of thyroid type 1 deiodinase activity by flavonoids. Food Chem Toxicol. 2002;40(7):913–917
  44. Köhrle J. Low dose competition of flavonoids with endogenous thyroid transport proteins: potential relevance to the thyroid hormone axis. In: Proceedings of the DFG functional food: safety aspects symposium. Wiley–VCH; 2004;p. 112–137
  45. Mori K, Stone S, Braverman LE, Devito WJ. Involvement of tyrosine phosphorylation in the regulation of 5′-deiodinases in FRTL-5 rat thyroid cells and rat astrocytes. Endocrinology. 1996;137(4):1313–1318
  46. Ebmeier CC, Anderson RJ. Human thyroid phenol sulfotransferase enzymes 1A1 and 1A3: activities in normal and diseased thyroid glands, and inhibition by thyroid hormones and phytoestrogens. J Clin Endocrinol Metab. 2004;89(11):5597–5605
  47. Persky VW, Turyk ME, Wang L, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr. 2002;75(1):145–153Erratum in: Am J Clin Nutr 2002;76(3):695
  48. Bruce B, Messina M, Spiller GA. Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food. 2003;6(4):309–316
  49. Cody V, Köhrle J, Auf’mkolk M, Hesch RD. Structure–activity relationships of flavonoid deiodinase inhibitors and enzyme active-site models. Prog Clin Biol Res. 1986;213:373–382
  50. Pedraza P, Calvo R, Obregon MJ, Asuncion M, Escobar del Rey F, Morreale de Escobar GM. Displacement of T4 from transthyretin by the synthetic flavonoid EMD 21388 results in increased production of T3 from T4 in rat dams and fetuses. Endocrinology. 1996;137(11):4902–4914
  51. Lueprasitsakul W, Alex S, Fang SL, et al. Flavonoid administration immediately displaces thyroxine (T4) from serum transthyretin, increases serum free T4, and decreases serum thyrotropin in the rat. Endocrinology. 1990;126(6):2890–2895
  52. Mendel CM, Cavalieri RR, Köhrle J. Thyroxine (T4) transport and distribution in rats treated with EMD 21388, a synthetic flavonoid that displaces T4 from transthyretin. Endocrinology. 1992;130(3):1525–1532
  53. Köhrle J, Fang SL, Yang Y, et al. Rapid effects of the flavonoid EMD 21388 on serum thyroid hormone binding and thyrotropin regulation in the rat. Endocrinology. 1989;125(1):532–537
  54. Munro SL, Lim CF, Hall JG, et al. Drug competition for thyroxine binding to transthyretin (prealbumin): comparison with effects on thyroxine-binding globulin. J Clin Endocrinol Metab. 1989;68(6):1141–1147
  55. Lim CF, Bai Y, Topliss DJ, Barlow JW, Stockigt JR. Drug and fatty acid effects on serum thyroid hormone binding. J Clin Endocrinol Metab. 1988;67(4):682–688
  56. Köhrle J, Spanka M, Irmscher K, Hesch RD. Flavonoid effects on transport, metabolism and action of thyroid hormones. Prog Clin Biol Res. 1988;280:323–340
  57. Auf’mkolk M, Köhrle J, Hesch RD, Cody V. Inhibition of rat liver iodothyronine deiodinase. Interaction of aurones with the iodothyronine ligand-binding site. J Biol Chem. 1986;261(25):11623–11630
  58. Vranckx R, Rouaze-Romet M, Savu L, Mechighel P, Maya M, Nunez EA. Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone. J Endocrinol. 1994;142(1):77–84
  59. Green NS, Foss TR, Kelly JW. Genistein, a natural product from soy, is a potent inhibitor of transthyretin amyloidosis. Proc Natl Acad Sci USA. 2005;102(41):14545–14550
  60. Neves FA, Cavalieri RR, Simeoni LA, et al. Thyroid hormone export varies among primary cells and appears to differ from hormone uptake. Endocrinology. 2002;143(2):476–483
  61. Zhang ZH, Wang Q. Modulation of a cloned human A-type voltage-gated potassium channel (hKv1.4) by the protein tyrosine kinase inhibitor genistein. Pflugers Arch. 2000;440(5):784–792
  62. Chu L, Zhang JX, Norota I, Endoh M. Differential action of a protein tyrosine kinase inhibitor, genistein, on the positive inotropic effect of endothelin-1 and norepinephrine in canine ventricular myocardium. Br J Pharmacol. 2005;144(3):430–442
  63. Auf’mkolk M, Köhrle J, Hesch RD, Cody V. Inhibition of rat liver iodothyronine deiodinase. Interaction of aurones with the iodothyronine ligand-binding site. J Biol Chem. 1986;261(25):11623–11630
  64. Köhrle J, Auf’mkolk M, Spanka M, Irmscher K, Cody V, Hesch RD. Iodothyronine deiodinase is inhibited by plant flavonoids. Prog Clin Biol Res. 1986;213:359–371
  65. Spanka M, Hesch RD, Irmscher K, Köhrle J. 5′-Deiodination in rat hepatocytes: effects of specific flavonoid inhibitors. Endocrinology. 1990;126(3):1660–1667
  66. Huang W, Wood C, L’Abbe MR, Gilani GS, Cockell KA, Xiao CW. Soy protein isolate increases hepatic thyroid hormone receptor content and inhibits its binding to target genes in rats. J Nutr. 2005;135(7):1631–1635
  67. Visser TJ. Pathways of thyroid hormone metabolism. Acta Med Austriaca. 1996;23(1/2):10–16[review]
  68. Rossi AM, Maggini V, Fredianelli E, Di Bello D, Pietrabissa A, Mosca F, et al. Phenotype–genotype relationships of SULT1A1 in human liver and variations in the IC50 of the SULT1A1 inhibitor quercetin. Int J Clin Pharmacol Ther. 2004;42(10):561–567
  69. Pacifici GM. Inhibition of human liver and duodenum sulfotransferases by drugs and dietary chemicals: a review of the literature. Int J Clin Pharmacol Ther. 2004;42(9):488–495[review]
  70. Masmoudi T, Hihi AK, Vazquez M, et al. Transcriptional regulation by triiodothyronine of the UDP-glucuronosyltransferase family 1 gene complex in rat liver. Comparison with induction by 3-methylcholanthrene. J Biol Chem. 1997;272(27):17171–17175
  71. Wisniewski AB, Cernetich A, Gearhart JP, Klein SL. Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice. Physiol Behav. 2005;84(2):327–334
  72. Adachi T, Ono Y, Koh KB, et al. Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice: toxicogenomic analysis using cDNA microarray. Food Chem Toxicol. 2004;42(3):445–452
  73. Nagao T, Yoshimura S, Saito Y, Nakagomi M, Usumi K, Ono H. Reproductive effects in male and female rats of neonatal exposure to genistein. Reprod Toxicol. 2001;15(4):399–411
  74. Köhrle J, Auf’mkolk M, Rokos H, Hesch RD, Cody V. Rat liver iodothyronine monodeiodinase. Evaluation of the iodothyronine ligand-binding site. J Biol Chem. 1986;261(25):11613–11622
  75. Cody V, Luft J. Structure–activity relationships of antiarrhythmic agents: crystal structure of amiodarone hydrochloride and two derivatives, and their conformational comparison with thyroxine. Acta Crystallogr B. 1989;45(Pt 2):172–178
  76. Schröder-van der Elst JP, van der Heide D, Köhrle J. In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats. Am J Physiol. 1991;261(2 Pt 1):E227–E232
  77. Chanoine JP, Alex S, Fang SL, et al. Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain. Endocrinology. 1992;130(2):933–938
  78. Schröder-van der Elst JP, van der Heide D, Rokos H, Köhrle J, Morreale de Escobar G. Different tissue distribution, elimination, and kinetics of thyroxine and its conformational analog, the synthetic flavonoid EMD 49209 in the rat. Endocrinology. 1997;138(1):79–84
  79. Schröder-van der Elst JP, van der Heide D, Rokos H, Morreale de Escobar G, Köhrle J. Synthetic flavonoids cross the placenta in the rat and are found in fetal brain. Am J Physiol. 1998;274(2 Pt 1):E253–E256
  80. Chang HC, Churchwell MI, Delclos KB, Newbold RR, Doerge DR. Mass spectrometric determination of genistein tissue distribution in diet-exposed Sprague–Dawley rats. J Nutr. 2000;130(8):1963–1970
  81. Doerge DR, Twaddle NC, Churchwell MI, Newbold RR, Delclos KB. Lactational transfer of the soy isoflavone, genistein, in Sprague–Dawley rats consuming dietary genistein. Reprod Toxicol. 2006;21(3):307–312
  82. Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Isoflavone content of infant formulas and the metabolic fate of these phytoestrogens in early life. Am J Clin Nutr. 1998;68(Suppl 6):1453S–1461S[review]
  83. Setchell KD, Zimmer-Nechemias L, Cai J, Heubi JE. Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet. 1997;350(9070):23–27
  84. Barrett JR. Soy and children's health: a formula for trouble. Environ Health Perspect. 2002;110(6):A294–A296
  85. Merritt RJ, Jenks BH. Safety of soy-based infant formulas containing isoflavones: the clinical evidence. J Nutr. 2004;134(5):1220S–1224S[review]
  86. Fitzpatrick M. Soy formulas and the effects of isoflavones on the thyroid. N Z Med J. 2000;113(1103):24–26[review]
  87. Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev. 2002;21(3/4):265–280[review]
  88. Sun Pan B, Kuo YY, Chen TY, Liu YC. Anti-oxidative and anti-inflammatory activities of two different species of a Chinese herb I-Tiao-Gung. Life Sci. 2005;77(22):2830–2839
  89. Thelen P, Scharf JG, Burfeind P, et al. Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer. Carcinogenesis. 2005;26(8):1360–1367
  90. Wuttke W, Seidlova-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas. 2003;44(Suppl 1):S67–S77
  91. Seidlova-Wuttke D, Hesse O, Jarry H, et al. Belamcanda chinensis and the thereof purified tectorigenin have selective estrogen receptor modulator activities. Phytomedicine. 2004;11(5):392–403
  92. Jarry H, Thelen P, Christoffel V, Spengler B, Wuttke W. Cimicifuga racemosa extract BNO 1055 inhibits proliferation of the human prostate cancer cell line LNCaP. Phytomedicine. 2005;12(3):178–182
  93. Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlova-Wuttke D. Chaste tree (Vitex agnus-castus)—pharmacology and clinical indications. Phytomedicine. 2003;10(4):348–357[review]
  94. Seidlova-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. J Steroid Biochem Mol Biol. 2003;86(2):179–188
  95. Weisskopf M, Schaffner W, Jundt G, Sulser T, Wyler S, Tullberg-Reinert H. A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines. Planta Med. 2005;71(10):910–916
  96. Nencini C, Giorgi G, Micheli L. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine 2006 [Epub ahead of print].
  97. Singh RP, Agarwal R. Prostate cancer prevention by silibinin. Curr Cancer Drug Targets. 2004;4(1):1–11[review]
  98. Raffoul JJ, Wang Y, Kucuk O, Forman JD, Sarkar FH, Hillman GG. Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer. 2006;6:107
  99. Cunha GC, van Ravenzwaay B. Evaluation of mechanisms inducing thyroid toxicity and the ability of the enhanced OECD Test Guideline 407 to detect these changes. Arch Toxicol. 2005;79(7):390–405
  100. Schmutzler C, Hamann I, Hofmann PJ, et al. Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney. Toxicology. 2004;205(1/2):95–102

PII: S0378-5122(06)00235-0

doi: 10.1016/j.maturitas.2006.06.013

Maturitas
Volume 55 , Pages S14-S25 , 1 November 2006

Article Tools

* Image Usage & Resolution