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

Maturitas

Volumn 55, Issue SUPPL. 1, 2006, Pages

  Hamann, Inka ^a   Seidlova Wuttke, D ^b   Wuttke, W ^b   Kohrle J ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

5 Deiodinase; Cimicifuga racemosa; Genistein; Isoflavonoid; Secondary plant metabolites; Soy; Thyroid hormone; Thyroperoxidase; Transthyretin

Indexed keywords

3',5' DIBROMO 4',6 DIHYDROXY 3 METHYLFLAVONE; APIGENIN; BELAMCANDA CHINENSIS EXTRACT; CARRIER PROTEIN; CIMICIFUGA RACEMOSA EXTRACT; DAIDZEIN; DITERPENE; F 21388; GENISTEIN; IODINE; ISOFLAVONOID; LYCOPUS EUROPAEUS EXTRACT; OXIDOREDUCTASE; PHYTOESTROGEN; PLANT EXTRACT; SELECTIVE ESTROGEN RECEPTOR MODULATOR; SILIBININ; SILYBUM MARIANUM EXTRACT; STEROID HORMONE; TECTORIGENIN; THYROID HORMONE; THYROID PEROXIDASE; THYROTROPIN; THYROXINE; THYROXINE DEIODINASE; UNCLASSIFIED DRUG; VITEX AGNUS CASTUS EXTRACT;

ARTICLE; CATABOLISM; CELL DIFFERENTIATION; CELL LEVEL; ENZYME ACTIVITY; ENZYME INHIBITION; FEEDBACK SYSTEM; GYNECOLOGIC DISEASE; HOMEOSTASIS AND REGULATION; HORMONE ACTION; HORMONE METABOLISM; HORMONE RELEASE; HORMONE SUBSTITUTION; HORMONE SYNTHESIS; HORMONE TRANSPORT; HUMAN; HYPOTHALAMUS HYPOPHYSIS SYSTEM; MOOD DISORDER; NONHUMAN; OVARIECTOMY; PERINATAL DEVELOPMENT; PLACENTA; PLANT METABOLISM; PREMENSTRUAL SYNDROME; SLEEP DISORDER; SOYBEAN; THYROID GLAND; THYROID HORMONE BLOOD LEVEL;

ANIMALIA; BELAMCANDA CHINENSIS; CIMICIFUGA RACEMOSA; SILYBUM MARIANUM;

EID: 33750618124     PISSN: 03785122     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.maturitas.2006.06.013     Document Type: Article

References (100)

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