The Thyroid Gland Lecture

Download Report

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 ).
Veena
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.
Veena
Contd. ..
THYROID GLAND HISTOLOGY
Veena
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
Veena
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.
Veena
THYROID HORMONES
OH
OH
I
I
I
I
I
O
O
NH2
I
O
Thyroxine (T4)
Veena
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
Veena
 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
Veena
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.
Veena
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.
Veena
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).
Veena
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.
Veena
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.
Veena
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)
Veena
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 :-
Veena
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
Veena
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.
Veena
Synthesis & Release
Veena

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.
Veena
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.
Veena
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.

Veena
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.
Veena
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 .
Veena
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
Veena
Mechanism of Action
Veena