1T2 The forgotten thyroid hormone Marc Harris ND.
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Transcript of 1T2 The forgotten thyroid hormone Marc Harris ND.
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T2T2
The forgotten thyroid hormoneThe forgotten thyroid hormone
Marc Harris ND
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Disclosure StatementDisclosure Statement
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I have no relevant financial or non-financial relationship(s) within the products or services described, reviewed, evaluated or compared in this presentation
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Early Thyroid Early Thyroid ResearchResearch
Late 1800’s
Thermogenesis
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Mid 1950Mid 1950’’ss
Uncoupling
Lardy, H.A and Feldcott, G. (1951)Ann. NY acad. Sci.,54, 636-648
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UncouplingUncoupling
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19601960’’ss
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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) Nature 193, 1058-1060
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Location of ActionLocation of Action
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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
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Iodothyronine deiodinaseIodothyronine deiodinase
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D1, D2, D3
D1, D2 D3
T4 > T3 rT3
T4 & T3
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T2T2
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•No further studies warranted
•Inactive
•Worthless metabolite
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19891989
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T3
Deiodinase inhibitor
T2
Deiodinase inhibitor
Horst,. Rokos H., and Seitz, H. J.(1989) biochem. J.261, 945-950
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T2T2
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3,5’- diiodothyronine
3 ’,5’- diiodothyronine
3,5 - diiodothyronine
3,3- diiodothyronine
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T2 Location of actionT2 Location of action
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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
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Beta OxidationBeta Oxidation
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T3, T2T3, T2
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•O2 consumption•Thermogenesis
Equivalent
T2 Peaked at 24 hours
T3 Peaked at 50-75 hours
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Hours 6-12 24-30 48 50-75 120
•T2 •T3
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Thyroid and MitochondriaThyroid and Mitochondria
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The cold rat study
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Cold exposed RatsCold exposed Rats
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T2 and T3 injected
Improved cold tolerance by different mechanisms
T3 acting on cellular DNA level
Lanni, A., Moreno, M., Lombardi A., and Goglia F. (1998) Pflugers Arch.-Eur J. Physiol., 436, 407-414,
T2 thought to directly interact with mitochondria
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T2 T2 in vitroin vitro
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Cellular energetics
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
Where does T2 work?
1. Proton motive force
2. Dissipation
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T2 Location in the mitochondrion
NADP > NADPH
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Cytochrome C Cytochrome C OxidaseOxidase
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G6PDG6PD
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Lombardi, A., Beneduce, L., Moreno, M., Diano, S., Colantuoni, V., Ursini, M. V., Lanni, A., and Goglia, F. (2000) Endocrinology,141, 1729-1734
G6PD and the Pentose Phosphate Pathway
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Aromatic Amino Aromatic Amino AcidsAcids
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Tyrosine Tryptophan
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Tyrosine/TryptophanTyrosine/Tryptophan
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Further tyrosine Further tyrosine metabolismmetabolism
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One more stepOne more step
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Pentose Phosphate Pentose Phosphate PathwayPathway
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•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
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GDPD RevisitedGDPD Revisited
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NADP > NADPH
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Calcium UptakeCalcium Uptake
Hummerich, H., and Soboll, S. (1989) Biochem. J.,258, 363-367
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Cellular calcium - the correct amount
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T2 functions - T2 functions - SummarySummary
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Increase B Oxidation
Increase G6PD
Stimulates Growth Hormone
Increases Metabolic Rate
Warms up Cold Rats
Regulates Calcium Uptake
Regulates Deiodinases
Complementary to T3 stimulation
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T2 DosageT2 Dosage
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1 mg/kg
120 pounder: 50 mg
200 pounder 90 mg
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AvailabilityAvailability
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Green Stone Swisswww.chemical-reagent.com
86-1-332-878-4921
Waterstone Techwww.waterstonetech.com
317-644-0862
Jinan Boss Chemical Industry Co., Ltd.www.chemboss.com.cn
Phone: 86-0531-585-91595Fax: 86-0531-863-30003
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Thyroid hormone T2
Facts are true until proven otherwise
Beliefs are true until proven otherwise
But, then they are still true
Author Unknown
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T2 - the forgotten T2 - the forgotten Thyroid HormoneThyroid Hormone
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Marc Harris ND702 N 19th AveBozeman MT 59718406-586-1997