This content explains the detailed multi-step process of thyroid hormone synthesis, starting from hormonal regulation by the hypothalamus and pituitary gland, and culminating in the production and release of T3 and T4 into the bloodstream.
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all right engineerd in this video we're
going to talk about the synthesis of
thyroid hormone all right so when we're
talking about the syn synthesis of
thyroid hormone what we're actually
doing in this video here is we're
actually taking the thyroid gland so you
know where the thyroid gland is actually
located it's located in the anterior
neck just inferior to the laryn or your
voice box and it's a butterfly shaped
gland and it consists of these things
called thyroid follicles those are the
structural and functional unit of the
thyroid gland what I'm doing is is I'm
taking a thyroid follicle and I'm
zooming in on it and taking a very deep
look into it okay so imagine this is the
thyroid follicle with these things
called follicular cells these simple
cuboidal epithelial cells I'm going to
zoom in on all of these cells and look
at the mechanism and the synthesis of
thyroid hormone okay all right so first
off we're going to go over the steps
afterwards we're going to have a quick
review and recap of everything we're
going to do first thing we're going to
start with is where is all of this whole
hormone producing action starting with
it's starting with the
hypothalamus so I like to remember it
like this I like to think about HPT axis
so hypothalamic
right because this is the
hypothalamus this is your anterior
pituitary right so we're going to put
anterior pituitary and then we're
zooming in on the thyroid gland right so
we're actually looking
specifically at the thyroid gland so I
like to think about this whole thing
we're going to talk about is the
hypothalamic pituitary thyroid axis okay
so let's go ahead and start about this
whole axis there's some neurons or
nuclei that's located in the actual
hypothalamus and these neurons are
secreting the actual a specific chemical
that's going to stimulate the anterior
pituitary what is those neurons these
neurons that are situated up here
that're going to be secreting this chemical
chemical called
called
thyrotropin releasing hormone TR these
nuclei are called the par
par ventricular
ventricular
nucleus okay so the PA of ventricular
nucleus is responsible for actually secreting
secreting
TR and if you know from the hypothalamic
anti pituitary video that the TR comes
down and stimulates these cells here in
the anterior pituitary what are those
cells there called these blue cells are called
called thyro
thyro
tropes and what happens is the TR
actually circulates down through that
blood connection that vascular
connection which is called the hypo
fisal portal system it circulates down
and goes into the anterior
pituitary stimulates these thyrotropes
and as a result these thyrotropes start
pumping out a specific type of hormone
that we're going to focus on a lot
called thyroid stimulating hormone
hormone
okay so the first hormone that was
produced was called thyrotropin
releasing hormone
TR the second hormone that was produced is
is
TSH what does TSH do it comes over here
to the thyroid gland in these thyroid
follicles so now look what TSH does it
actually circulates through the
blood and it comes over and it binds
onto this receptor that's present on the
external face of the cell membrane
because you know TSH is actually a
peptide hormone so it doesn't have
receptors inside the cell it has
receptors outside the cell when this TSH
binds onto this
receptor it activates an intracellular
pathway it activates specifically a g
stimulatory protein that that g
stimulatory protein is normally bound to
GDP which keeps it off but then it's
bound to GTP which turns it on so then
it's bound to GTP and it becomes
active the G stimulatory protein then
goes and activates a eector enzyme and
enzyme is going to react with the G
stimulatory protein and this enzyme is
called a denate
cyclas and what does AD denate cyclas do
this G stimulatory protein activates the
adate cyclace and aenl cyclas converts ATP
ATP
into cyclic
am then cyclic activates a specific
enzyme and this enzyme is called protein
kinas a here's where it gets good you
know there's transcription factors you
know transcription factors are
specifically proteins that have one
component so let's say I draw a
transcription Factor here let's say I
draw it in red here's a transcription
Factor here's a little pocket
here and here is going to be the part
that binds with the DNA protein cyas a
comes over and puts phosphates on this
transcription Factor so look what it
does it comes in here and puts
phosphates onto this transcription
Factor when it phosphor relates this
transcription factor that transcription
Factor starts stimulating the genes to
make a specific protein so you know
whenever there's transcription
transcription produces what's called
mRNA and then that mRNA will actually go
to the ribosomes on the rough ER right
and produce proteins those proteins when
they're actually made they via
translation those proteins are modified
and and changed here and actually have
different types of actions that are
occurring here in the rough VR then
after that they're actually sent to to
the gii and then they're packaged and
modified within the GGI and then what
the gii is going to pack those this
protein inside of a vesicle and then
these vesicles that you're actually
going to make so out of this GOI you're
going to pack that actual that protein
right there into this vesicle so now I'm
going to pack that protein into this
vesicle so there's my protein and then
what's going to happen is I'm going to
take this protein and I'm going to fuse
this vesicle with the cell membrane so
now look this vesicle here is going to
fuse with the cell membrane because this
vesicle is a lipid bil layer this is a
lipid by layer they can come together
and dissolve right so fuse one another
when that fuses look what happens here
after the fusion of that vesicle so now
you get this little inward bubble and
what are you going to start releasing
out of here you're going to release out
into this luminal space here this
protein so then you're going to release
out this protein Okay so
that was the step there that was the
step of synthesizing this basic unit of
thyroid hormone okay stimulates a
receptor activates protein KY a
intracellularly phosphor transcription
factors stimulates the genes to make a
specific protein transcribes it
translates it packages it and excretes
it out or exocytosis it into the Lumen
now what we're going to do is we're
going to zoom in on this protein we're
going to take this protein and zoom in
on it what is this protein called this
protein is
called thyroglobulin thyro
thyro
globulin so what did we synthesize
essentially we we synthesized this
thyroglobulin colloid because it's like a
a
colloid here's where we have the basic
unit of our thyroid hormone what do I
mean by that you see these I drew
circular amino acids I'm going to
represent the the circular amino acids
in this case are going to
represent a specific amino acid and this
amino acid that I want it to be is called
called
tyrosine if we're talking about tyrosine
we could we could show its structure
let's say here's its structure right
here uh you have an AM Amino
Terminus carbon with a hydrogen and then
a carboxy Terminus and then you got
this phenol group coming off of it okay
that's the basic structure of tyrosine
but we're going to denote it by these
circles okay
now we have the basic unit here now we
need to do some other things so what
else do we need for this reaction to
occur we actually need iodine okay but
where's iodine coming from it's going to
come from certain types of nutrient
sources now generally here in America we
usually put it in the salt right it's
like iodized salt but it's in a lot of
other food sources but generally it's
circulating here in the blood so let's
show it here circulating in the
bloodstream let's do that in Black
so let's say here is our
iodine but usually
iodine in the blood is in an ion form
meaning that it has a negative charge so
it's not really iodine this is actually
called iodide so we have to be specific about
about
this this is
iodide now iodide is extremely
concentrated in this area so we can say
that this is high concentration right so
high concentration of iodine over here
and I can just instead of putting high I
can put high like that up arrow and over
here there's a very low concentration of
iodine so to pump something from areas
of low to high requires energy
thankfully we have sodium sodium is so
good to us look what sodium says he's like
like
hey iodide I got you I'll help you out
so what sodium does is he moves you know
sodium he's an actually lower
concentration ins inside the cell and
then he's actually in high concentration
outside the
cell so you know what he does he moves
from areas of high to low that's a
passive transport when you're moving
from high to low well guess who else
moves with him co-transporting iodide so
iodide moves with him okay so there's a
sorter or co-transporter where you're
removing sodium and iodide it doesn't
directly use ATP it's an indirect use of
ATP what is it called when there's an
indirect use of ATP this right here is called
called secondary
secondary active
active
transport okay so now we got the iodide
in here why do we need the iodide okay
this iodide is going to come through the
cell let's keep following it here let's
see what it does and look what happens
here there's a specific protein here on the
the
membrane let's say here's this protein
here and look what this Pro this protein
it might seem like it's not it's
insignificant but this protein is very
important because obviously any mutation
it can alter the the function of the
thyroid hormone production so let's say
here in red we draw this protein
here okay what is this here protein
called this protein is called pendrin
it's called pendrin so what is it called
again it's called
pen dren
and what it does is it pumps the iodide
out here into this vicinity okay so now
the iodide is going to get pumped out
here into this actual luminal space so
now look iodide is going to get
pumped out but here's the next thing
that has to
happen this is reactive okay because
it's got all this charge we want to be
able to you know prevent it from having
all these problems so that we can put it
on this uh amino acid
so look what this enzyme here look at
this little sneaky Frenchman enzyme
looks like right so look at this guy
with the you know the whole like little
mustache right this enzyme is a really
cool enzyme this enzyme is called
thyroid peroxidase I'm going to denote
as TPO but again I'll write it here it's called
called thyroid
peroxidase what this enzyme does is
Imagine here's his foot imagine here's
this guy is g to kick the iodide he's
going to kick him and what he's going to
do is he's going to kick him so hard
that he converts this
guy into what's called
iodine so you know what uh you know
whenever you go from iodine which is a
negative charge to a zero charge that's
called oxidation so what is this this
reaction here this is oxidation
oxidation is the loss of electrons he
kicks him so hard he knocks electrons
off of them okay so look at this here he
kicks them so hard knocks electrons off
of them what is this step right here
called this step is called iodide
iodide
oxidation okay then he's got this other
enzyme he's
got he's only got four toes and then
look what he does he takes let's say
there's a whole bunch of iodines here he
takes these iodines and he has them on
his toes here and look what he does he
comes over and he puts boop boop boop
onto these little tires amino acids so
look what he does he takes these iodines
and he puts them onto these tyrosine
amino acids so what does he do then
let's say that he puts let's say he puts
an iodine here and an iodine there an
iodine there an iodine there he put four
iodines on these guys this right here is
called iodination so when the thyroid
peroxidase puts the iodines on the
tyrosine amino acids of the
thyroglobulin colloid this is called
dination all right but then he can do
that to other ones too so let's say that
he does it also to this guy here so
let's say he puts on one there and let's
say he puts two onto this
one okay you see what he did there this
is where it gets really cool now let's
apply a concept when you're naming
things generally you use the term like
mono to say one die to say two right so
how many amino acids are on that
tyrosine two we don't say say two we say
d but what is d d
iodo tyrosine amino acid what about this
one same thing it has two of them so di
ioto tyrosine amino acid what about this
one he has one so that's mono so this is
mono ioto tyrosine amino acid this one
has two so this is D ioto tyrosine amino
acid look what this guy does he has a
handle over
here he's so cool that he can actually
split his hand in half look at this he
splits it in half he goes over here and
splits this guy in half and then he
takes his little fingers and he fuses
these guys together so then look what he
can do he can couple the dit and the dit
and couple the MIT and the dit if he
couples these guys together he fuses
them together what are you going to get
let's see if I take a
dit a diot thyrosine and I add it to a
diot thyrosine I'm going to get four
iodines on one on these two tyrosine
amino acids we're going to call that
T4 T4 is another word for
thyroxine okay but what if I take an
MIT and a dit and fuse these together
well then I get three iodines on two
tyrosine amino acids so we're going to
call that
T3 T3
is also called trodo
trodo thyronine
thyronine
okay thyroxine and triot thyronine so T3
and T4 collectively are thyroid
thyroid
hormone okay that should make sense now
right so iodide oxidation iodination
coupling now there's other enzymes in
this area that will try to be able to to
help in this cutting and re uh uh moving
these different types of dits and mits
around thyroid globula but in general
thyroid peroxides is helping to be able
to kind of put these dits and mits
together but there will be other
cleavage processes and
rearrangements but we've basically in a
nutshell have t T4 and T3 in our
thyroglobulin colloid but we can't just
secrete that out into the blood we have
to get these chunks and these chunks out
of this
so now look guys we have this guy here
here's our thyroid globulin with the T4
and T3 in it our thyroid hormone what
we're going to do is we're going to take
this whole thyroglobulin choid with the
T4 and T3 and bring it into the cell you
see these guys right here these
lysosomes they're going to help us to
get this thyroid hormone out of the
colloid so how does it do this how does
it get in you know there's a process
where you take substances into the cell
it's called
endocytosis so what do this guy going to
do he's going to bring so it's going to
actually endocytose this whole protein
and put it into this vesicle so what is
this this reaction right here called
whenever you bring this protein
substance into the cell and pack it into
this vesicle this is going to be called Endo
Endo
cytosis okay now we've brought it into
the cell and we have our T4 T3 right
there so this is T4 this is T3 but the
whole thing is the thyroglobulin colloid
right and our T4 and T3 are part of that
we have to isolate that T4 and T3 out of
that so that we only secrete that how do
we do that these Lal enzymes the lomes will
will
fuse with this vesicle here so look it
fuses with the vesicle and then these
enzymes are ready to start cutting
things up they're ready what are they
going to
do they're going to cut all around this
thyroglobulin CID and isolate just the
T4 and just the T3 so now what are we
going to get out of this afterwards all
we're going to have left in this vesicle
so now what we're going to do is we're
going to isolate out of this these
two things here the T3 and the T4 so
let's say this one up top is the T4 so
it'll have four iodines coming off of
it okay then over here let's say this is
T3 so I'll have
three iodines coming off of it right so
we isolated the T4 and the T3 out of the
thyroglobulin colloid through the action
losal
enzymes then we have our functional T3
and T4 now we're going to fuse this
vesicle with the cell membrane of the
follicular cell when this fuses look
what we can do we can release
out this T3 and T4 out into the
bloodstream but you know T3 and T4 are
kind of interesting they're kind of um
they act like steroid hormones so
because of that these are actually
because of those Benzene Rings the
phenol rings they're not really good at
being water soluble so we have to
transport them in the blood through some
type of transport protein so the liver
actually synthesizes a specific protein
here to transport
this actual thyroid hormone through the
actual blood what is this protein here
called that it actually secretes this
protein here is called
thyroxine binding
globulin okay so this protein right here is
is called
called thyroxine
thyroxine binding
binding
globulin and what happens is look now
I'm going to draw over here I'm just
going to write it in T4
and T3 are transported by this protein
called thyroxine binding globulins
okay all right so now that we've done
that we have almost everything that we
need here to make the functional thyroid
hormone now we're going to do is is
we're going to recap everything and
we're going to finish this video off
okay guys so let's recap in an order
here so the first thing that had to
happen was TR had to be released so
from
hypothalamus and specifically you could
say the paraventricular
nucleus TR then stimulates the anter
pituitary so the thyrotropes but we're
release
TSH then TSH
stimulates the pH cells right so our
thyroid gland so specifically the
follicular cells that make up that
synthesize thyroglobulin so I'm going to
put here
thyroglobulin so tgb
thyroglobulin okay then what the fourth
step was is that we had to get that
iodide inside so we had to do what's called
called
okay that was the fourth step the fifth
step was that we had to oxidize we had
to oxidize the iodide right so we have
oxidation of
iodide through the thyroid peroxidase enzyme
enzyme
right after it gets transported through
the pendrin protein into the actual
Lumen then the sixth step is we have to
iodinate the tyrosine amino acids so
iodination of
tyrosine amino acids okay seventh step
is coupling so then you have to couple
so then you have to
couple what the
dits and
mits respectively dit with MIT is T3 dit
with dit is
T4 then what the eighth step is I have
to take that thyroglobulin coll my T3
and T4 and bring it into the cell so I
have to mediate what's called Indo
Indo
cytosis okay of T what
thyroglobulin and with well with the T3
and the T4 so in other words we have to
endocytose of the thyro globulin
with T3 and T4 in it then losal enzymes lysosomal
lysosomal
enzymes cleave
T3 and T4 out of
thyroglobulin and what is the 10th and
final step the 10th and final step is
actually going to be the EXO
EXO
cytosis of T3 and T4 into blood
plasma which is bound to the actual thy
thyroxine binding globulins which is
then going to be transported to the
Target tissues all right guys in this
video we covered the synthesis of
thyroid hormone I hope it made sense I
hope you guys enjoyed it in the next
video we're going to talk about the
effect of thyroid hormone on its Target organs
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