Transcript The Thyroid Gland Lecture

Ms Veena Shriram
Introduction

Described first by Thomas Wharton
(1616-1673)

Largest Endocrine Gland

Weighing 15 – 20 g

Highly Vascular ( 5 ml / g / min ).
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Functional Anatomy
•Thyroid : shield
• Two lobes are connected by
isthmus infront of the larynx
•Receives highest rate of blood
flow per gram of tissue
•Histologicaly made up of
multiple of closed follicles
(acini): 100 – 300 µm.
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Contd. ..
THYROID GLAND HISTOLOGY
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http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html
•
Follicles are lined with single layer of cuboidal
epithelial cells, which secrete into interior .
•
Filled with proteinaceous matter: colloid, made up
of large glycoprotein thyroglobulin containing thyroid
hormones within it.
Inactive gland:
Follicles - large
Colloid – abundant
Cells lining are flat
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Active gland:
Follicles - small
Cells lining are cuboid
Reabsorption lacunae
seen
Fetal Thyroid

From 12th week of gestation fetal thyroid begins
to secrete hormones.

Th. Hormones (T. H.) are essential for normal
growth & development of fetal CNS , skeletal
systems.

Maternal TSH & thyroxine cannot cross placental
barrier, however iodine can cross the barrier.

Fetal T. H. production depends on ant. pituitary &
fetal hypothalamus.
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THYROID HORMONES
OH
OH
I
I
I
I
I
O
O
NH2
I
O
Thyroxine (T4)
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OH
NH2
I
O
OH
3,5,3’-Triiodothyronine (T3)
Synthesis & secretion of T. H.
1. Iodide Trapping
2. Formation & secretion of thyroglobulin
3. Oxidation of iodide ions
4.
a) Iodination of tyrosine
b) Organification of TG
5. Storage of TG
6. Release of T.H. : T4 & T3
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 93 % hormone secreted by T. gland is Thyroxine (T4).
 7 % is triiodothyronine (T3).
 T3 is:

4 times more
potent than T4

present in smaller
quantities

Persists for shorter
time than T4
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Iodine Metabolism

Iodine is a raw material for T. H. synthesis.
Ingested iodine is converted into iodide
Daily avg. intake of iodine is 500 µg/ day .
Min. daily intake to maintain normal T. function 150 µg/ d
Normal plasma iodine level is about 0.3 µg/ dL .

To prevent iodine deficiency common table salt is iodized with 1 part




Na iodide to every 1,00,000 parts of NaCl.

Fate of Ingested iodides: absorbed from GIT into blood.
1/5th is taken up by T. gland and rest is excreted by
kidneys.
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1. Iodide Pump (Iodide Trapping)

Food iodide from blood is , taken up by the follicular
cells of thyroid – a process called iodide trapping.

Thyroid cells RMP is -50 mV compared to interstitial
fluid & luminal colloid.

The T. cell membrane facing capillaries contain a
+
-
symporter or iodide pump : Na / I symporter (NIS)

It works against electrochemical gradient & traps
iodide by secondary active transport mechanism.

It concentrates the iodide 30 – 250 times than in the
blood.
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2. Formation & secretion of thyroglobulin

T. cells are typical protein secreting glandular cells.

ER & GA synthesize & secrete into the follicles, a
large glycoprotein molecule : thyroglobulin (TG - with
MW 3,35,o00)

TG contains about 70 tyrosine amino acids.

Tyrosine combines with iodide to form T. H. ( within
TG molecule).
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3. Oxidation of Iodide ions

Conversion of the iodide ions to an oxidized
form of iodine (either nascent iodine, I0 or I-3) by
the enzyme peroxidase in presence of H2O2.
 Peroxidase is attached to apical membrane of the
cell.

This oxidized form of iodine can combine with
the a. a. tyrosine.
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4. a) Organification of thyroglobulin
1.
Organification of thyroglobulin (TG):
The
binding of iodine with TG molecule is called
organification.
2.
Oxidized iodine in presence of enzyme
iodinase binds very rapidly with
thyroglobulin.
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ION TRANSPORT BY THE
THYROID FOLLICULAR CELL
ClO4
-,
SCN-
Perchlorate, thiocynate depress I
transport by competitive inhibition
BLOOD
I-
I-
NaI symporter (NIS)
Thyroid peroxidase (TPO)
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organification
COLLOID
Propylthiouracil (PTU)
blocks iodination of
thyroglobulin
4.
b)
Iodination of Tyrosine
Tyrosine + oxidized iodine
monoiodotyrosine(MIT)
I0 or I-3
diiodotyrosin (DIT)

Coupling :-
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MIT + DIT
Triiodotyrosine (T3)
DIT + MIT
RT3
Biosynthesis of TH
.
qq
qq
Organification
IApical membrane
Peroxidase
I-
Golgi
I-
E.R.
I-
trap
Basal membrane
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I-
.
Storage & Release of TG
5.
STORAGE
 After synthesis of TH , TG molecules contain
up to 30 molecules of T4 & few molecules of T3

2-3 months requirement is stored.
6. RELEASE



The follicle cells engulf a little TG (containing T4 &
T3) by endocytosis (by formation of reabsorption
lacunae).
TG is digested by proteinase and T4 & T3 are set
free
After cleaving of T4 & T3 from TG, free H is
released into capillaries.
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Synthesis & Release
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
3/4th of iodinated tyrosine in the TG never
becomes TH, but remains MIT, DIT.

During digestion of TG for release of T4 &
T3 , iodinated tyrosins are also freed from
TG, but not released into blood

Instead I is cleaved by deiodinase enzyme.
Thus recycling I.

Congenital absence of this enzyme lead to I
deficiency.
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Daily Rate of Secretion

93 %
T4

7%
T3 is released.

Later half of the T4 is slowly deiodinated
to T3

Finally T3 is mainly delivered to & used
by tissues, a total about 35 µg / d.
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Transport of TH In The Blood
Approximately 99 % of T4 is bound to
3 plasma proteins: Thyroxine binding
globulin (TBG) ~75%; Thyroid binding
prealbumin (TBPA or transthyretin) 1520 %; albumin ~5-10 %
 Only ~0.02% of the total T4 in blood is
unbound or free.
 Only ~0.4% of total T3 in blood is free.

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Slow release of T4 & T3 to the
tissues

T4 & T3 are released slowly to the tissues
because of high affinity with TBG of T4

Half quantity of T4 is released in 6 days
and that of T3 in 1 day

After entering tissues again it binds with
protein & used slowly.
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Slow onset & long duration of action

This is due to binding with proteins both in
plasma & tissue cells, and due to the way they
act.

T3 is 4 times rapid than T4 .
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Mechanism of Action

transcription of large no. of genes, therefore
large no. of proteins, enzymes, & other substances
are synthesized.

generalized
in functional activity

High affinity of intracellular TH receptor for T3

TH activate nuclear receptors (TRα on gene 17 &
TRβ R on gene 3 ) & initiate the transcription process.
 mRNA formation, then RNA translation
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Mechanism of Action
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