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Costanzo Physiology (Chapter 9C) Endocrine Physiology: Thyroid Hormone || Study This!

hello and welcome to the next portion of
the endocrine physiology chapter
going over the thyroid hormones in the
thyroid gland
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so going over our thyroid hormones this
is produced by the
follicular epithelial cells within the
thyroid gland itself
we have two types of thyroid hormones
we've got t4 and t3
t3 is the metabolically active
hormone within the actual cell itself
but
t4 is more abundant in the plasma so
it's almost
stored as t4 and the plasma goes into
the cell and it gets converted to t3
within the cell
to then have its actions the difference
between
t3 and t4 is just the amount of iodine
within the molecule
so t4 means that there's four iodine
molecules within
that hormone whereas t3 has three iodine
molecules so that's the major difference
between the two
so going into how the thyroid hormone
gets produced within the thyroid gland
first we should look at the anatomy of
the thyroid gland within the thyroid
gland we have these thyroid follicles
which is essentially a ring of
follicular epithelial cells
which secrete colloid into the lumen
this colloid contains thyroid hormone
attached to a molecule called
thyroglobulin
when the gland gets stimulated to
secrete thyroid hormone
that thyroid hormone within the colloid
then gets endocytosed into the cell
and then excreted via the follicular
cells into
the blood vessels so now we should talk
about how thyroid hormone actually gets
produced within the follicular
epithelial cell that's shown here in
figure 9.18 here and all the specific
steps
so the first step is actually getting
iodine into the cell since that's the
major component of thyroid hormone
interestingly the thyroid gland is the
only gland that actually uses iodine so
all your dietary iodine
goes to your thyroid gland to get
incorporated
into thyroid hormone so via the sodium
co-transporter here
iodine gets transported into the
follicular epithelial cell
and this transporter actually gets
upregulated if we have iodine deficiency
to help shuttle even more iodine into
the cell
this is against its concentration and
electrical gradient so
it's quite a push it requires a lot of
energy to actually get the iodine into
the cell
clearly if there is a severe iodine
deficiency then we will have a lack of
iodine going into the cell
and then a reduced production of our
thyroid hormone but this
transporter tries to combat it initially
by up regulating in the presence of mild
deficiency
now once iodine enters the cell it then
gets oxidized
into an i2 molecule via what's called a
thyroid peroxidase this thyroid
peroxidase is going to come
up a couple times but you'll see that
within the follicular lumen now we have
our oxidized iodine as i2 now this i2
will then
bind with a thyroglobulin molecule which
comes from the cell
being synthesized from a tyrosine
molecule so the combination of iodine
with thyroglobulin
is called organification and then that
creates this molecule which is
thyroglobulin with either an
mit or dit mit stands for
mono iodine tyrosine and then dit stands
for diado tyrosine basically
mit means there's one iodine with that
tyrosine molecule on the thyroglobulin
dit means there's two iodines so at this
stage we then have another peroxidase
reaction
which will combine these molecules to
create t4 and t3
so if we combine two dits then we're
going to end up with t4
if we combine the dit with an mit then
we're going to end up with t3
because that's simple maths we're just
adding on iodine together so then we end
up with four iodines in the case of t4
and then three iodines in the case of t3
there is also some residual mit and dit
molecules
left on this thyroglobulin so this is
the kind of final product that sits
within the follicular lumen
which is this thyroglobulin with
attached t4
and then some mit and dit so this just
sits in the follicular lumen
waiting for the stimuli to secrete t4
so once that stimulus occurs which
predominantly is the secretion of
thyroid stimulating hormone from that
anterior pituitary gland
then this thyroglobulin complex is going
to get endocytosed
into the follicular cell and then it's
going to release
its t4 and t3 into circulation
that thyroglobulin tyrosine molecule is
going to get recycled
so is the mit and dit releasing its
iodine to then get recycled back
into this equation again so that is the
entire production
of thyroid hormone remember t4 is the
most prevalent molecule in the plasma
but then t3 is the more metabolically
active so once
in the circulation these thyroid
hormones actually bind to something
called
thyroxine binding globulin so the
majority of our thyroid hormone is
actually
bound to proteins within the plasma and
that means that it's almost
stored in the plasma for the cells the
free
hormones are the only physiologically
active hormones
so if we have less of this globulin
molecule that means more of the thyroid
within the plasma is going to be in the
free active
form so we may have less globulin and
hepatic failure which is the organ that
actually produces these globulins which
means we have more of the active t4 t3
in the plasma
that actually gets sensed by the
anterior pituitary gland
which means that we secrete less thyroid
stimulating hormone as a negative
feedback mechanism
so we actually reduce the amount of
thyroid gland secretion in that
situation
whereas if we have an increased level of
globulins so then it's actually
holding more of that thyroid hormone in
the plasma as
non-active or protein-bound thyroid
hormone which is going to happen let's
say in pregnancy which inhibits hepatic
breakdown of this globulin
that means that there is less active t43
that is free within the blood the
anterior pituitary gland senses that and
thinks that we have
a relative thyroid deficiency so then
it's going to release
more tsh to increase the secretion of
thyroid hormone
once the thyroid hormone actually enters
the cell remember predominantly
it's going to be t4 that enters the cell
since that is more abundant
in our plasma the target tissue will
then convert that t4
into active thyroid hormone as in t3
using the enzyme 5-ironase now that will
also produce some of this reverse
t3 which is inactive but the active
component is
t3 now during starvation when you don't
have many nutrients and you are not
producing that much energy
and you need to reduce your metabolic
rate then you will inhibit
this five iodine enzyme to reduce your
metabolic rate
by reducing the amount of active thyroid
hormone in your target cells
because thyroid hormone the whole thing
about it is that it actually
increases our metabolic rate so if
you're in the starvation
state you need to conserve energy you're
going to produce
less active thyroid hormone so then your
cell is going to have a lower basal
metabolic rate that gets us to the
regulation of hormone secretion we've
already talked about the globulin levels
so if you have
increased globulin levels then you're
going to increase the secretion of your
thyroid hormone because there's less
free hormones and vice versa thyroid
stimulating hormone is clearly the main
stimulation for secretion from the
thyroid glands and then thyroid
stimulating immunoglobulins
is another molecule which basically acts
like tsh at the receptor of the thyroid
gland
and that's actually a cause for
hyperthyroidism called graves disease
which is just
excessive production of this thyroid
stimulating immunoglobulin
which tells the thyroid gland to produce
a lot of
thyroid hormone so you end up in a
hyperthyroid state
in terms of inhibitory factors obviously
if you have severe iodine deficiency you
don't have enough iodine to incorporate
into your thyroid hormones you could
have deficiency of that drnas
which releases t4 and t3 from your
thyroglobulin ironically excessive
iodine intake actually
inhibits the organification of iodine to
a thyroglobulin
which is also an inhibitory factor and
then lastly any medications that's going
to inhibit
the movement of iodine into the cell or
inhibit those peroxidase enzymes which
create the thyroid hormone themselves
so next up we're going to talk about the
actual actions of thyroid hormones
the easiest way to think about this is
that thyroid hormone gets into the cell
activates the nuclear receptor via t3
and then that causes the increased
synthesis of new proteins via
transcription and translation
so thyroid hormone will get into the
cells
and increase the metabolism of that cell
so whatever that cell may be
it's just going to increase the
metabolic rate of that cell so it's
going to cause growth
of our organs it's going to cause bone
maturity
it's going to cause maturation of our
central nervous system
in our cardiovascular system it's going
to increase our cardiac output because
it gets into the myocardial cells
basically increases the enzymes or
calcium recycling
increases our contractions increases the
beta receptors on the cells so then
they're more likely to get stimulated by
the sympathetic nervous system
and increase cardiac output it increases
metabolism just because it increases the
cycling of glucose we're increasing the
protein production to increase glucose
absorption
to produce glucose increase lipolysis
increase protein synthesis and
degradation ultimately it actually
has a net catabolic effect on protein
degradation because your entire body
is basically just churning through its
metabolic processes it's just trying to
work as hard as possible
it increases our basal metabolic rate by
increasing the production of our sodium
potassium atpase
transporters which just increases the
amount of
oxygen consumption because we need to
produce a lot of atp
to now feed these increased sodium
potassium atpases
so oxygen consumption goes up a lot of
energy gets used
we increase our heat production due to
that increased use of
energy and then our basal metabolic rate
increases
so the typical clinical signs of someone
with excessive
thyroid hormone which is up regulating
all of these cells basal metabolic rate
is going to be an increased hunger but
yet weight loss because you're just
chewing through all that extra energy
and excitability or irritability
obviously the opposite is also true if
you don't have enough thyroid hormone
then your basal metabolic rate is going
to reduce everything's going to reduce
so you're going to become lethargic
sluggish and gain
weight now it does go into some of the
causes of hyperthyroidism and
hypothyroidism
for people the main cause of
hyperthyroidism so high thyroid gland is
that graves disease remember we
increase the level of our thyroid
stimulating immunoglobulins
if you have high of those that means
that you're going to produce a lot of t4
and t3 that's going to have a negative
feedback
on your anterior pituitary gland so your
tsh is going to be low and that's the
same if you have a thyroid gland
neoplasia that's producing excessive
thyroid
hormone so you can sometimes use thyroid
stimulating hormone levels as a
telltale to see what's going on
obviously if you've got something that's
increasing t43 production
independent of tsh that's going to have
a negative feedback on tsh
and you'll have low tsh levels obviously
if you have hyperthyroidism however due
to
increased tsh levels then your tsh is
going to be high in addition to your
thyroid hormones but that happens much
less commonly when it comes to
hypothyroidism the most common reason is
immune disruption of our thyroid glands
or thyroiditis
so that's going to reduce your t4 and t3
levels which via negative feedback is
going to increase your tsh levels
because tsh is going to say why aren't
we producing any t4 and t3
so tsh is going to be high t4 t3 is
going to be low
another clinical sign associated with
hypothyroidism is
mixed edema which is increased
filtration of fluid
out of your capillaries causing edema of
the subcutaneous tissues
because of increased osmotically active
muco-polysaccharides within your
interstitial fluid
when it comes to treatment it's rather
self-explanatory for hypothyroidism
you're just going to do hormone
replacement therapy by giving thyroid
hormone
for the treatment of hyperthyroidism
high thyroid hormone
then there's three real options
medications to inhibit the synthesis of
thyroid hormones
surgical removal of the thyroid gland or
radioactive
ablation that's when you give
radioactive iodine since the thyroid
gland is the only gland that uses iodine
then you just only have radioactivity
within the thyroid gland which kills off
only the thyroid gland so those are our
treatment options
now the last thing we'll talk about here
is goiter goiter just
means that the thyroid gland has
enlarged
and that's going to occur whenever we
have high levels of
trophic hormones which includes tsh
and also thyroid stimulating
immunoglobulin
so any thyroid abnormality where we have
increased tsh
or increased thyroid stimulating
immunoglobulin is going to stimulate the
growth of the thyroid gland
usually we have increased tsh either
because of a tumor
in the anterior pituitary gland which is
uncommon
or because we have low t4 tsh levels
with very low negative feedback to our
interior pituitary gland
so that's going to be the end of this
video for today i hope you enjoyed it
feel free to join in for the next one
where we are going to talk about our
adrenal glands feel free to drop a
comment otherwise we'll see in the next
one