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The forgotten thyroid hormone

T2. The forgotten thyroid hormone. Marc Harris ND. 1. Disclosure Statement. I have no relevant financial or non-financial relationship(s) within the products or services described, reviewed, evaluated or compared in this presentation. 2. Early Thyroid Research. Late 1800 ’ s.

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The forgotten thyroid hormone

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  1. T2 • The forgotten thyroid hormone Marc Harris ND 1

  2. Disclosure Statement I have no relevant financial or non-financial relationship(s) within the products or services described, reviewed, evaluated or compared in this presentation 2

  3. Early Thyroid Research Late 1800’s Thermogenesis 3

  4. 4

  5. Mid 1950’s Uncoupling Lardy, H.A and Feldcott, G. (1951)Ann. NY acad. Sci., 54, 636-648 5

  6. Uncoupling 6

  7. 1960’s Tata • 1st considered transcription • T3 injected to hypothyroid rats • Increased metabolic rate • Actinomycin D • No increase in metabolism Tata, J. R., Ernster, L., and Lindberg, O. (1962) Nature193, 1058-1060 7

  8. Location of Action Cellular binding sites for T3 Extra nuclear actions Oppenheimer, J. H., Koerner, D., Schwartz, H. L., aand Surks, M.I. (1972) J. Clin. Endocrinol. Metab., 35, 330-333 Oppenheimer, J. H., Schwartz, H.L., Mariash, C.N., Kinlaw, W. B., Wong, N. C. W., and Freake, H.C., (1987) Endocrine Rev., 8, 288-308 8

  9. Iodothyronine deiodinase D1, D2, D3 D3 D1, D2 T4 & T3 T4 > T3 rT3 9

  10. 10

  11. T2 • No further studies warranted • Inactive • Worthless metabolite 11

  12. 1989 T3 Deiodinase inhibitor T2 Deiodinase inhibitor Horst,. Rokos H., and Seitz, H. J.(1989) biochem. J. 261, 945-950 12

  13. T2 3,5’- diiodothyronine 3’,5’- diiodothyronine 3,3- diiodothyronine 3,5 - diiodothyronine 13

  14. T2 Location of action T3 And T2 administered to hypothyroid rats Energy expenditure measured by RER T3 and T2 had equivalent metabolic stimulation Deiodinase inhibited T2 stimulation of Beta Oxidation Cimmino, M., Mion, F., Goglia, F., Minaire, Y., and Geloen, A. (1996) J. Endocrinol., 149, 319-325 14

  15. Beta Oxidation 15

  16. T3, T2 • O2 consumption • Thermogenesis Equivalent T2 Peaked at 24 hours T3 Peaked at 50-75 hours 16

  17. T2 • T3 Hours 6-12 24-30 48 50-75 120 17

  18. Thyroid and Mitochondria The cold rat study 18

  19. Cold exposed Rats T2 and T3 injected Improved cold tolerance by different mechanisms T3 acting on cellular DNA level T2 thought to directly interact with mitochondria Lanni, A., Moreno, M., Lombardi A., and Goglia F. (1998) Pflugers Arch.-Eur J. Physiol., 436, 407-414, 19

  20. T2 in vitro Cellular energetics Where does T2 work? 1. Proton motive force 2. Dissipation Lombardi, A., Lanni, A., Moreno, C., M., and Goglia, F., (1998) Biochem. J., 330 521-526 Brand, M.D. (1997)J. Exp, Biology., 200 193-202 20

  21. T2 Location in the mitochondrion NADP > NADPH 21

  22. Cytochrome C Oxidase 22

  23. G6PD G6PD and the Pentose Phosphate Pathway Lombardi, A., Beneduce, L., Moreno, M., Diano, S., Colantuoni, V., Ursini, M. V., Lanni, A., and Goglia, F. (2000) Endocrinology,141, 1729-1734 23

  24. Aromatic Amino Acids Tyrosine Tryptophan

  25. Tyrosine/Tryptophan

  26. Further tyrosine metabolism

  27. One more step

  28. Pentose Phosphate Pathway • Nucleotide biosynthesis • Detoxification • Reduction of oxidized • glutathione • Cytochrome P450 • monooxygenases • Central Brain Processing • Synthesis of ATP • Fatty acid biosynthesis • Cholesterol biosynthesis • Thyroid hormone production • Serotonin production • Dopamine Production 28

  29. GDPD Revisited NADP > NADPH 29

  30. Calcium Uptake Hummerich, H., and Soboll, S. (1989) Biochem. J.,258,363-367 Cellular calcium - the correct amount 30

  31. T2 functions - Summary Increase B Oxidation Regulates Deiodinases Complementary to T3 stimulation Increase G6PD Stimulates Growth Hormone Warms up Cold Rats Increases Metabolic Rate Regulates Calcium Uptake 31

  32. T2 Dosage 1 mg/kg 120 pounder: 50 mg 200 pounder 90 mg 32

  33. Availability Green Stone Swiss www.chemical-reagent.com 86-1-332-878-4921 Waterstone Tech www.waterstonetech.com 317-644-0862 Jinan Boss Chemical Industry Co., Ltd. www.chemboss.com.cn Phone: 86-0531-585-91595 Fax: 86-0531-863-30003 33

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  35. Thyroid hormone T2 Facts are true until proven otherwise Beliefs are true until proven otherwise But, then they are still true Author Unknown 35

  36. T2 - the forgotten Thyroid Hormone Marc Harris ND 702 N 19th Ave Bozeman MT 59718 406-586-1997 36

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