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:^ Water^ soluble
hormones^ Receptor
:^ membrane receptorReceptor:^ membrane^
receptor Hormone^ + Recep:
Activate^ G ‐ protein
(transducin)
on^ innerside
of^ membrane ActivatePhosphlipase^ C adenylcyclase
Second^ messengers
IP^3 DAG CAMP Third messenger
release of ca++from ER
activate protein kinase C
activate protein kinase A
Third^ messenger
release^ of^ ca++from
ER^ activate^ protein
kinase^ C^ activate
protein^ kinase
A
++^ Ca +calmodulin
Phosphorylation
Phosphorelation Activate^ protein
kinase^ dependant
on^ ca/calmodulinPhosphorylation
Diseases resulting from receptor defect:
g^
p
Biosynthesis
of^ peptide
Hormones:
Parathyroid
H^ as^ an
example
Steps:Steps:
1.^ initiation
►^ formation
of^ a^ mRNA
Specify^ a
polypeptide
larger^ than
required
one^2
On ribosome
translation
On^ ribosome
translation
20 aminoacyl
residue^ (p
eptide)formed
(signal^ peptide) y^
(p p^ )^
(^ g^ p p
3.^ Signal
peptide facilitate
‐ growing
polypeptide
chain
‐ associated
mRNA
Ribosome to ER ‐ Ribosome
to^ ER Contnued^ to^ next^ slide
THYROID HORMONES
Structure and biosynthesis of
T^ and
T
Structure
and^ biosynthesis
of^ Tand T^3
4 Steps:
1 ‐^ Iodide uptake from blood energy dependent uptake inhibited 1 ‐^ Iodide
uptake^ from
blood^ energy
dependent
uptake^ inhibited by^ perchlorate
2 ‐^ iodide
►^ free
radicle^ I
iodination on tyrosine molecules which present on surface of 3
iodination
on^ tyrosine
molecules
which^ present
on^ surface
of
thyroglobulin
by^ peroxidese
on^ position
3 mono
iodotyrosin
thereon^
position^
5 di^ iodiotyrosin 4 ‐^ by^ peroxidese
Coupling will take place between 2 diiodotyrisine
►^ T
Coupling will
take^ place
between
2 diiodotyrisine
►^ T^4
Or^ between
monoand&
diiodotyrosine
►^ T
Both T3&T4 will be on the surface of thyroglobulinBoth^ T^3 &T
4 will^ be
on^ the^ surface
of^ thyroglobulin^ Contnued
to^ next^ slide
by^ effect^ of
TSH
Th^ l b li
t^ f^
d b^ i^
t^ i
Thyroglobulin
transferred
by pinocytosis from^ colloid 6 ‐^ Thyroglobulin
vesicle^ fuse
with^ lysosome
►^ proteolysis
T3,^ T4^ ,^ mono
and^ diiodotyrosine
7 ‐^ T4:^ T3^20 ‐^30 :
T3 ►^^3 ‐^5 times
more^ potent
than^ T T4^ deiodinase
T
In prepreferal tissueIn^ prepreferal
tissue^ T4T Prohormone
true^ hormone
Plasma transport of T
3 and T
Plasma
transport
of^ T^3
and^ T
>^ 99.5%^
are^ boundd
Binding^ proteins:
Thyroxine‐binding
globulin^ • Albumin^ • Precalbumin^ TBG prealb albumin
T4^70
20 %^
T4^70
T3^38
35 % Protein bound^ are
biologically
inactive►
Reserve
g^ y Inactivation
of^ T3^ &T
T4^ deiodination
T3^ +^ rT
T3,^ rT3^ deiodinated
bis^ ‐iodothyronines
3 P^ i h
l h^
i
3.^ Peripheral
hormone
conversion
by^ conversion
of^ T^4 into
active^
T^3 or^ inactive
T^
f^ i t
f^ h^
i l^ i
rT^3 as^ a
response
of^ a^ variety
of^ physiologic
and^ pathologic
changes
and^ determining
the
b l^
b t^
h^
ti^ ti^
d
balance
between
hormone
activation
and
inactivation,
e.g.^ malnutrition,
liver^ disease,
li^ d d bilit
t^
d
generalized
debility,
pregnancy,
stress^ and steroid^
therapy
increase
rT^3
