T2 slides Marc Harris ND

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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
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Early Thyroid Research
Late 1800’s
Thermogenesis
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Mid 1950’s
Uncoupling
Lardy, H.A and Feldcott, G. (1951)Ann. NY acad. Sci.,
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54, 636-648
Uncoupling
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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) Nature 193, 1058-1060
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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
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Iodothyronine deiodinase
D1, D2, D3
D3
D1, D2
T4 & T3
T4 > T3
rT3
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T2
•No further studies warranted
•Inactive
•Worthless metabolite
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1989
T3
Deiodinase
inhibitor
T2
Deiodinase
inhibitor
Horst,. Rokos H., and Seitz, H. J.(1989) biochem. J.
261, 945-950
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T2
3,5’- diiodothyronine
3’,5’- diiodothyronine
3,3- diiodothyronine
3,5 - diiodothyronine
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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
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Beta Oxidation
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T3, T2
•O2 consumption
•Thermogenesis
Equivalent
T2 Peaked at 24 hours
T3 Peaked at 50-75 hours
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•T2
Hours
6-12 24-30
•T3
48
50-75
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120
Thyroid and Mitochondria
The cold rat study
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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,
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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
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T2 Location in the
mitochondrion
NADP > NADPH
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Cytochrome C Oxidase
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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
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Aromatic Amino Acids
Tyrosine
Tryptophan
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Tyrosine/Tryptophan
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Further tyrosine
metabolism
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One more step
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Pentose Phosphate Pathway
• Synthesis of ATP
• Fatty acid biosynthesis
• Cholesterol biosynthesis
• Thyroid hormone production
• Serotonin production
• Dopamine Production
•
•
•
•
•
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Nucleotide biosynthesis
Detoxification
Reduction of oxidized
glutathione
Cytochrome P450
monooxygenases
Central Brain Processing
GDPD Revisited
NADP > NADPH
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Calcium Uptake
Cellular calcium - the correct amount
Hummerich, H., and Soboll, S. (1989) Biochem. J.,258, 363-367
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T2 functions - Summary
Increase B Oxidation
Regulates Deiodinases
Increase G6PD
Complementary to T3
stimulation
Stimulates Growth Hormone
Warms up Cold Rats
Increases Metabolic Rate
Regulates Calcium Uptake
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T2 Dosage
1 mg/kg
120 pounder: 50 mg
200 pounder 90 mg
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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
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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
Thyroid Hormone
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Marc Harris ND
702 N 19th Ave
Bozeman MT 59718
406-586-1997
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