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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

Aromatic Amino Aromatic Amino AcidsAcids

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Tyrosine Tryptophan

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