Structure of the T. Hormones

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Structure of the T. Hormones
NH3
T4 3,3,5,5-L-tetraiodothyronine
LKS
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Structure of the T. Hormones
NH3
T3 3,5,3-L-triiodothyronine
LKS
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Structure of the T. Hormones
NH3
rT3 3,3,5-L-triiodothyronine
LKS
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Control of Thyroid Function

• TRH - TSH - Thyroid Gland Control
• Autoregulation of Active Hormone Release
• Peripheral Deiodination of T4 to T3

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TRH - TSH - T3 , T4
SRIH

• Hypothalamus (Cold Stimulus)

TRH
Other Sites
(-)
()
TSH
T3 , T4
Thyroids
LKS
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TSH Control of Thyroid Gland

• Rapid Effects (2-5 min.)
• Ca, cAMP
• Colloid Reabsorption
• Intermediate Effects (10-30min.)
• Blood Flow to thyroid (vasodilatation)
• Na-K-ATPase Activity
• Na Transport into Thyroid
• Slow Effects (/- 2 hours)
• Glucose Uptake Utilization
• Iodide Transport
• O2 Uptake Utilization
• A. A. Uptake, RNA, DNA, Prot. Synt.

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TSH Control of Thyroid Gland

• Long Term Effects (Days, Weeks, Months)
• Blood Supply
• Number of Cells (hyperplasia)
• Size of Cells (hypertrophy)
• Amount of Colloid
• SUMMARY
• TH output, TH Synthesis Storage

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Other Controls over Thyroids

• LATS- Long Acting Thyroid Stimulator
• IgG autoantibody against thyroid gland
• Peak Actions at 12 hours
• HTSI- Human Thyroid Stimulating Immunoglobulin
• Peak actions at 30 minutes
• EPS- Exopthalmus Producing Substance
• 50 of LATS Patients have EPS also

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Autoregulation of Hormone Release
LKS
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Wolff-Chaikoff Effect
-
P
Cell
I Cell
I
Shuts Down Thyroid
Transport
T.H. Output towards Normal
Cell Sensi. to TSH
Thyroid Can Escape From Effects (weeks)
LKS
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Peripheral T4 Conversion to T3
T3
5-Deiodinase
5-Deiodinase
T4
T2
5-Deiodinase
5-Deiodinase
rT3
LKS
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The Thyroid Gland and Cells
Colloid (T hyroglobulin)
Thyroid Peroxidase H2O2..
Reabs.
Prot.
I
Lysosomes
cAMP
Ca
R
T3 , T4
I
TSH
TSH
Plasma
LKS
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Cells
Colloid
T.P. H2O2
MIT
T3
I
Tyr Residues

T4
DIT
-
I
A.A.
T.P. H2O2
T3,T4
A.A.
-
I
LKS
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Cells
T.P. H2O2
Extracellular
I
I
I
I
I
I
I
I
Colloid
I

I
I
THYROGLOBULIN
I
I
I
-
I

T.P. H2O2
T3,T4
A.A.
-
I
LKS
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T3 and T4 Transport in Plasma
T3 T4
Free Hormone Conc. 70-180 ng 4-11 ug
1.1-2.8x10-9M 5-14x10-8M
Plasma Protein Binding
Thyroid Binding Globulin (TBG)
70 - 70-75 75
99.6 99.96
LKS
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Thyroid Hormone Target Tissues

• Skin Appendages
• Eyes
• Cardiovscular System
• Respiratory System
• Developing C.N.S.
• Skeleton
• G.I. Tract
• Musculature
• Renal System

• Blood Protein Cmpnt.
• Pituitary (GH,ACTH)
• Adrenals 1o Catechols
• Female Reproductive
• Developing Tissues
• ENERGY METABOLISM
• Not Affected Adult Brain, Spleen, Retina, Testes

LKS
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Thyroid Hormone Actions
GENERAL
O2 Consumption T3 12-18 hours, Peak _at_ 24
hrs T4 36 - 48 hrs, Peak _at_ 72 hrs Affects
DNA, RNA,Cell , Cell Size in all (to 2 yrs)
THERMOREGULATION
LKS
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Thyroid Hormone Actions 2
T.H. Protein Metab. Carbohydrate Metab. Fat
Metab.
Synergistic with other hormones, such as Insulin,
Glucagon, Growth Hormone, Epinephrine,
Norepinephrine, Glucocorticoids,PTH, VitD
Use and NEED, NO Storage
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Physiology of the Thyroid Hormones
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Physiology of the Thyroid Hormones
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Physiology of the Thyroid Hormones