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8/10/2019 K4A - Fisiologi Tiroid
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FISIOLOGI HORMON
METABOLIK TIROID
dr. Tri Jauhari P, SpPD, MBiomed, MSc
Bagian Fisiologi/Ilmu Penyakit Dalam
FK UNSOED/RSMS
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PENDAHULUAN
Sistem endokrin: sistem kontrol tubuh,kelenjar, darah,organ target,tanpasaluran
Respon lambat : menit, jam,bulan, atautahun.
Komunikasi: melalui media yaitu
HORMON ("pembawa pesan melaluialiran darah ke berbagai sel)
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PENDAHULUAN
Sifat hormon: Bekerja spesifikpada organ, bagian tubuh
tertentu atau aktivitas tertentu
Dihasilkan tubuh dalam jumlah yang sangat
sedikit tetapi memiliki pengaruh besarterhadap aktivitas tertentu dalam tubuh
Bekerja lambat,pengaruh hormon tidakspontan seperti pada pengaturan oleh
syaraf
Sebagai senyawa kimia, hormon tidakdihasilkan setiap waktu. Hormon diproduksihanya apabila dibutuhkan
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Introduction.
Thyroid gland maintains levels of metabolism intissues.
Thyroid hormones stimulate oxygen consumption inmost cells of the body.
Regulates lipid and CHO metabolism. Necessary for normal growth and maturation.
Absence causes mental and physical slowing.
Excess causes body wasting nervousness tachycardiaand tremors.
Controlled by Thyroid stimulating hormones(TSH)
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Formation and secretion of thyroid hormones.
The principal hormones secreted by thyroid gland are
Thyroxine(T4) and triiodothyronine(T3)
T3 is also formed in the peripheral tissue by
deiodination of T4 Both hormones are iodine-containing amino acids.
T3 is more active than T4
Calcitonin is also produced by thyroid in response toincreased calcium levels.
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Structure of thyroid hormones
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Thyroglobulin.
T3 and T4 are synthesized in the colloid by iodination
The hormones are bound to thyroglobulin within thethyroid cells
Thyroglobulin is also synthesized in the thyroid cells
The hormones remain bound to thyroglobulin untilsecreted
When secreted, the colloids is ingested by thyroidcells, peptide bonds are hydrolyzed and free T3 and
T4 are discharged into the system
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Iodine Metabolism
Iodine is the raw material for thyroid hormone
synthesis.
Ingested iodine is converted to iodide and
then absorbed
The principal organs that take up the iodide
are the thyroid which uses it to make thyroid
hormones and the kidneys which excrete it in
the urine.
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Iodide trapping
Thyroid concentrates iodide by activelytransporting it from circulation to the colloid
The transport mechanism is called iodide
trapping mechanism or the iodide pump The pump is an example of a secondary active
transport system
In the gland, iodide is oxidized and bound totyrosine.
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Thyroid Hormone synthesis
In the thyroid, iodide is oxidized to iodine and boundwithin secs to tyrosine attached to thyroglobulin
The enzyme responsible for the oxidation andbinding of iodide is Thyroid peroxidase
Monoiodotyrosine (MIT) is next iodinated toDiiodotyrosine(DIT)
2 DIT molecules undergo oxidative condensation toform Thyroxine(T4)
T3 is probably formed by condensation of MIT andDIT.
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Synthesis and Secretion of the Thyroid Metabolic Hormones
Iodine is Required for the Formation of Thyroxine
a. Iodine in the form of iodides; 1.0 mg/wk
b. Of the iodide absorbed from the intestine, 80% israpidly excreted by the kidneys, and 20% is
selectively removed by cells of the thyroid gland
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Synthesis and Secretion of the Thyroid Metabolic Hormones
Iodide Pump-the Sodium-Iodide Symporter
(Iodide Trapping)
Fir. 76.2 Thyroid cellular mechanisms for iodine transport, thyroxine and
triiodothyronine formation, and thyroxine and triiodithyronine
release into the blood
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Synthesis and Secretion of the Thyroid Metabolic Hormones
Iodide Pump-the Sodium-Iodide Symporter
(Iodide Trapping)
a. Transport of iodine from the bloodb. Formation and secretion of thyroglobulin by the
thyroid cells
c. Oxidation of the iodide ion
d. Iodination of tyrosine and formation of the thyroidhormone (organification of thyroid)
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Synthesis and Secretion of the Thyroid Metabolic Hormones
e. Storage of thyroglobulin-enough is stored to last the
body for 2-3 months
f. Release of throxine and triiodithyronine-cleaved from
the thyroglobulin and then released into the blood
g. Daily rate of secretion; 93% is normally thyroxine and
7% triiodothyronine. However, about of thethyroxine is slowly deiodinated to form the T3 so the
tissues get mainly T3
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Synthesis and Secretion of the Thyroid Metabolic Hormones
h. Thyroxine and triodothyronine are transported bound
to plasma proteins
i. Because of the high affinity to the plasma proteins,
the hormone is released very slowly
j. Thyroid hormones have slow onset and long duration
of action
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Synthesis and Secretion of the Thyroid Metabolic Hormones
Fig. 76.4 Approximate prolonged effect on the basal metabolic rate caused by
administering a single large dose of thyroxine
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Transport and metabolism of Thyroid
Hormones
Large amounts of T3 and T4 are bound to plasma proteins.
The unbound T3 and T4 are the physiologically active forms of the
hormones.
Free T3 and T4 inhibit the secretion of TSH.
The plasma proteins that bind thyroid hormones are
albumin,transthyretin and thyroxin-binding globulin(TBG)
Most of the circulating T4 is bound to TBG
T3 is bound to albumin
TBG levels are increased in estrogen-treated patients and
pregnant women
TBG levels are reduced by glucocorticoids and androgens.
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Physiological Functions of the Thyroid Hormones
Thyroid Hormones Increase the Transcription of
Large Numbers of Genes
a. Most of the thyroxine secreted by the thyroid is
converted to triiodothyronine (T3)
b. Thyroid hormones activate nuclear receptors
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Physiological Functions of the Thyroid Hormones
Fig. 76.5 Thyroid hormone
activation of target cells
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Physiological Functions of the Thyroid Hormones
Thyroid Hormones Increase Metabolic Activity-
(increase the BMR 60-100x)
a. Thyroid hormones increase the number and activityof mitochondria
b. Increase the active transport of ions through the
cell membrane (sodium and potassium)
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Physiological Functions of the Thyroid Hormones
Thyroid Hormones Effect on Growth
a. Promote the growth and development of the brain
during fetal life and first years of postnatal life
b. Deficiency will retard growth during growing
years
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Physiological Functions of the Thyroid Hormones
Effect on Specific Bodily Mechanisms
a. Stimulation of cbh metabolism-rapid uptake of
glucose, enhanced glycolysis, enhanced gluconeo-genesis, increased rate of absorption, increased
insulin secretion
b. Stimulation of fat metabolism-lipids are mobilizedrapidly decreasing fat stores, increases free fatty
acid concentration in plasma, and accelerates the
oxidation of free fatty acids in cells
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Physiological Functions of the Thyroid Hormones
Effect on Specific Bodily Mechanisms
c. Increased thyroid hormone decreases the
concentrations of cholesterol, phospholipids, andtriglycerides in plasma and vice versa; increases
the cholesterol secretion in bile
Increased Requirement for Vitamins
Increased Metabolic Rate
Decreased Body Weight
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Physiological Functions of the Thyroid Hormones
Fig. 76.6 Approximate relation of daily rate of thyroid hormone
(T4 and T3) to the basal metabolic rate
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Physiological Functions of the Thyroid Hormones
Effect on the Cardiovascular System
a. Increased blood flow and cardiac output
b. Increased heart ratec. Increased heart strength
d. Normal arterial pressure
Increased Respiration Increased Gastrointestinal Motility
Excitatory Effects on the CNS
Muscles React With Vigor
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Physiological Functions of the Thyroid Hormones
Muscle Tremors with Hyperthyroidism
Difficulty in Sleeping and Constant Tiredness
With Hyperthyroidism
Increased Thyroid Hormone Increases theSecretion of Several Other Endocrine Glands
Needs to be Normal for Normal Sexual Function
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Regulation of Thyroid Hormone Secretion
TSH (Anterior Pituitary) Increases Thyroid Secretion
a. Increased proteolysis of the thyroglobulin
b. Increased activity of the iodide pumpc. Increased iodination tyrosine
d. Increased size and secretory activity of the thyroid
cells
e. Increased number of thyroid cells
Cyclic AMP Mediates the Stimulatory Effect of TSH-
acting as a second messenger system
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Regulation of Thyroid Hormone Secretion
Secretion of TSH is Regulated by Thyrotropin-
Releasing Hormone from the Hypothalamus
Feedback Effect of Thyroid Hormone to Decrease
the Secretion of TSH
Fig. 76.7 Regulation of thyroid secretion
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w
TRH
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Regulation of Thyroid Hormone Secretion
Diseases of the Thyroid
a. Hyperthyroidism-Graves Disease, toxic goiter
b. Symptoms of hyperthyroidism
1) High state of excitability
2) Intolerance to heat
3) Mild to extreme weight loss
4) Varying degrees of diarrhea
5) Muscle weakness
6) Extreme fatigue
7) Tremor of the hands
8) Exophthalmos
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Regulation of Thyroid Hormone Secretion
Diseases of the Thyroid
c. Hypothyroidism-endemic colloidal goiter caused by
iodine deficiency
a. Symptoms of hypothyroidism
1) Myxedema
2) Cretinism
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Iodine deficiency
When dietary intake drops,thyroid hormones
synthesis is inadequate and secretion is
reduced.
TSH is increased and thyroid hypertrophies
producing an iodine deficiency Goiter.
Endemic goiter-mountainous areas..
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Iodine deficiency.
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Cretinism
Children with hypothyroidism from birth are calledcretins
They have reduced growth and mentally retarded.
Potbellies
Enlarged protruding tongue
Causes-
Maternal iodine deficiency
Fetal thyroid dysgenesis
Inborn errors of thyroid synthesis
Maternal antibodies that cross placenta
Fetal hypo pituitary hypothyroidism
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Clinical correlates.
Signs and symptoms of hypo or hyper thyroidism areconsequences of effect of thyroid hormones.
Hypothyroidism-
Syndrome of hypothyroidism is called myxedema.
Term also used to describe skin changes inhypothyroidism.
May be end result of secondary pituitary failure (pituitaryhypothyroidism)
May be due to hypothalamic failure( hypothalamichypothyroidism)
May be due to thyroid disorder.
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EXAMPLES OF THYROID DISEASES
Hypothyroidism Hyperthyroidism
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goiter
cretinism
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There are two biologically active thyroid hormones:
- tetraiodothyronine (T4; usually called thyroxine)
- triiodothyronine (T3)
Derived from modification of an amino acid (tyrosine)
Thyroid Hormones
Diff b t T4 d T3
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The thyroid secretes about 80 micrograms of T4, but only
5 micrograms of T3per day.
However, T3 has a much greater biological activity (about
10X) than T4.
An additional 25 micrograms/day of T3 is produced by
peripheral monodeiodinationof T4.
T4
thyroid
I-
T3
Differences between T4 and T3
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Thyroid hormones are unique biologicalmolecules inthat they incorporate iodine in their structure.
Thus, adequate iodine intake (diet, water) is requiredfor normal thyroid hormone production.
Major sources of iodine:
- iodized salt- iodated bread
- dairy products
Minimum requirement: 75 micrograms/day
US intake: 200 - 500 micrograms/day
Why is Iodine Important in Thyroid Hormone Production?
I di M t b li
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Dietary iodine is absorbedin the GI tract, then taken up
by the thyroid gland (or removed from the body by thekidneys).
The transportof iodide into follicular cells is dependent
upon a sodium/iodine cotransport system.
Iodide taken up by the thyroid gland is oxidizedby
peroxide in the lumen of the follicle:
peroxidaseI- I+
Oxidized iodine can then be used in production of
thyroid hormones.
Iodine Metabolism
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The Next Step: Production of T3 or T4
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The follicle cells of the thyroid produce thyroglobulin.
Thyroglobulinis a very large glycoprotein.
Thyroglobulinis released into the colloid space,
where its tyrosine residues are iodinated by I+
. This results in monoiodotyrosine (MIT) or
diiodotyrosine (DIT).
The first Step: Production of thyroglobulin
Initial Steps in Thyroid Hormone Synthesis
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follicle
cell
extracellular space
colloid space
I-
I-
thyroglobulinwith
monoiodotyrosines and
diiodotyrosines
iodination
thyroglobulin
thyroglobulin
gene
I+oxidation
I-Na+ Na+K+
Initial Steps inThyroid Hormone Synthesis
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The iodinated tyrosine residues on thyroglobulin are
modified and joined to form T3 and T4, still attached
to the thyroglobulin molecule.
Second step: Production of Thyroid Hormones
from Iodinated Thyroglobulin
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In order to secrete T3/T4, the thyroglobulin in the
colloid space is internalized by endocytosisbackinto the follicle cell.
This internalized vesicle joins with a lysosome,whose enzymes cause cleavage of T3 and T4 fromthyroglobulin. Some T4 is converted to T3 at this
point.
T3 and T4 are then released into the extracellularspace by diffusion.
Only minute amounts of thyroglobulin arereleased into the circulation.
Utilization of Thyroglobulin to Secrete Thyroid Hormones
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Utilization of Thyroglobulin to Secrete Thyroid Hormones
folliclecell
colloid space
endocytosis
thyroglobulin
T3 T4
colloid droplet
lysosome
T3/T4
(deiodinated, recycled)
extracellular space
(T4 T3)
Transport of Thyroid Hormones
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Thyroid hormones are not very soluble in water(but are lipid soluble).
Thus, they are found in the circulation associatedwith binding proteins:
- Thyroid Hormone-Binding Globulin(~70% ofhormone)
- Pre-albumin (transthyretin), (~15%)- Albumin(~15%)
Less than 1% of thyroid hormone is found free inthe circulation.
Only free and albumin-bound thyroid hormone isbiologically available to tissues.
Transport of Thyroid Hormones
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Transthyretin (TTR) is a serum and
CSF carrier of the thyroxine (T4) and
retinol. This is how transthyretin
gained its name, transports thyroxineand retinol.
TTR was originally called
prealbumin because it ran faster than
albumins on electrophoresis gels.
In CSF it is the primary carrier of T4,
as albumin is not present. TTR also
acts as a carrier of retinol (vitamin A)
through an association with retinol-
binding protein (RBP).
Transthyretin (prealbumin, amyloidosis type I)
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T3 has much greater biological activity than T4.
A large amount of T4 (25%) is converted to T3 inperipheral tissues.
This conversion takes place mainly in the liverand
kidneys. The T3 formed is then released to theblood stream.
In addition to T3, an equal amount of reverse T3may also be formed. This has no biological
activity.
Conversion of T4 to T3
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T4
R
3,3-T2
R
T3
Step up
R
rT3
Step down
THYROID HORMONE METABOLISM
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Three deiodinases (D1, D2 & D3)catalyze thegeneration and/disposal of bioactive thyroid hormone.
D1 & D2 bioactivate thyroid hormone by removing
a single outer-ring iodine atom.
D3 inactivates thyroid hormone by removing a
single inner-ringiodine atom.
All family members contain the novel amino acid
selenocysteine (Se-Cys) in their catalytic center.
THYROID HORMONE DEIODINASES
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NH2extracellular domain
intracellular domainCOOH
BASIC ORGANIZATION OF THE
SELENODEIODINASES
EXISTS AS ADIMER
Se-Cys
Thyroxine and its precursors: Structure & Synthesis
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Thyroid hormones are made from tyrosine and iodine
Thyroxine and its precursors: Structure & Synthesis
Thyroxine and its precursors: Structure & Synthesis
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Thyroid hormone synthesis
Thyroxine and its precursors: Structure & Synthesis
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The thyroid gland is capable of storing manyweeks worth of thyroid hormone(coupled tothyroglobulin).
If no iodine is available for this period, thyroidhormone secretion will be maintained.
One Major Advantage of this System
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Thyroid hormone synthesis and secretion isregulated by two main mechanisms:
- an autoregulation mechanism, whichreflects the available levels of iodine
- regulation by the hypothalamus and anteriorpituitary
Regulation of Thyroid Hormone Levels
A t l ti f Th id H P d ti
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The rate of iodine uptake and incorporation into
thyroglobulin is influenced by the amount ofiodide available:
- low iodide levels increase iodine transportinto
follicular cells
- high iodide levels decrease iodine transportinto
follicular cells
Thus, there is negative feedback regulationof iodide
transport by iodide.
Autoregulation of Thyroid Hormone Production
Neuroendocrine Regulation of Thyroid Hormones:
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Thyroid-stimulating hormone (TSH) is produced by thyrotroph cells
of the anterior pituitary. TSH is a glycoprotein hormone composed of two subunits:
- alpha subunit (common to LH, FSH, TSH)
- TSH beta subunit, which gives specificity of receptor binding andbiological activity
a
LHbFSHb TSHb
LH FSH TSH
Role of TSH
Feedback regulation
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Feedback regulation
the hypothalamic-pituitary-thyroid axis
Hormones derived from the pituitary thatregulate the synthesis and/or secretion of other
hormones are known astrophichormones.
Key players for the thyroid include:
TRH - ThyrotropinReleasing Hormone
TSH - Thyroid Stimulating Hormone
T4/T3- Thyroid hormones
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T3 & T4 Control Pathways
& Diseases from Malfunction
Action of TSH on the Thyroid
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TSH acts on follicular cells of the thyroid.
- increases iodide transportinto follicular cells
- increases production and iodination of thyroglobulin- increases endocytosis of colloidfrom lumen into follicular cells
Na+
I-thyroglobulinfolliclecell
gene
I-
endocytosis
thyroglobulin
T3 T4
colloid droplet
I-I+iodinationthyroglobulin
Na+ K+
ATP
y
1
2
3
Mechanism of Action of TSH
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TSH binds to a plasma membrane-bound, G protein-coupled receptor on thyroid follicle cells.
Specifically, it activates a Gs-coupled receptor, resulting inincreased cyclic AMPproduction and PKAactivation.
TSH
Gsa
Adenylyl
Cyclase
ATP cyclic AMP
Protein kinase
A
Follicle cell
ec a s o ct o o S
Regulation of TSH Release from the Anterior Pituitary
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TSH release is influenced by hypothalamic TRH, and bythyroid hormones themselves.
Thyroid hormones exert negative feedback on TSH releaseat the level of the anterior pituitary.
- inhibition of TSH synthesis
- decrease inpituitary receptors for TRH
hypothalamus
TRH
TRH receptor
TSH synthesispituitary T3/T4
+
--
g y
Regulation of TSH Release from the Anterior Pituitary
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Thyrotropin-releasing hormone (TRH) is a hypothalamicreleasing factor which travels through the pituitary portal
system to act on anterior pituitary thyrotroph cells. TRH acts through G protein-coupled receptors, activating
the IP3 (calcium) and DAG (PKC) pathways to causeincreased production and release of TSH.
TRH phospholipase C
G protein-coupled
receptor
IP3 calcium
DAG PKC
calmodulin
Thyroid hormones also inhibit TRH synthesis.
Negative Feedback Actions of Thyroid Hormones on
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hypothalamus
TRH
TRH receptor
TSH synthesispituitary
T3/T4
+
--
-
TRH synthesis
TSH Synthesis & Release
PITUITARY-THYROTROPE CELL
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TSH regulation of
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TSH binds to specific cell surface receptors thatstimulate adenylate cyclase to produce cAMP.
TSH increases metabolic activity that is required to
synthesize Thyroglobulin (Tg)and generate peroxide. TSH stimulates both I-uptakeand iodination of
tyrosine resides on Tg.
TSH regulation of
thyroid function
I t t b th th id f lli l ll
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Ion transport by the thyroid follicular cell
I- I-organification
Propylthiouracil (PTU) blocksiodination of thyroglobulin
COLLOID
BLOOD
NaI symporter (NIS)
Thyroid peroxidase (TPO)
PTU, a thioamide drug used to treat hyperthyroidism
THYROGLOBULIN SYNTHESIS IN THE
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IodinationofTyr residues of Tg
COLLOID
TSH
TSH receptorTPO
THYROGLOBULIN SYNTHESIS IN THE
THYROID FOLLICULAR CELL
THYROID HORMONE SECRETION BY THE
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THYROID HORMONE SECRETION BY THE
THYROID FOLLICULAR CELL
COLLOID
TSHTSH receptor
DIT
MIT I-
T4T3
Other Factors Regulating Thyroid Hormone Levels
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Diet: a high carbohydrate diet increasesT3 levels,resulting in increased metabolic rate (diet-induced
thermogenesis).
Low carbohydrate diets decreaseT3 levels, resulting in
decreased metabolic rate.
Cold Stress: increases T3 levels in other animals, but
not in humans.
Other Factors Regulating Thyroid Hormone Levels
Actions of Thyroid Hormones
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Required for GH and prolactin production & secretion
Required for GH action
Increases intestinal glucose reabsorption (glucose
transporter)
Increases mitochondrial oxidative phosphorylation (ATP
production)
Increases activity of adrenal medulla (sympathetic;
glucose production)
Induces enzyme synthesis
Result: stimulation of growth of tissues and increased
metabolic rate.
Actions of Thyroid Hormones
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Thyroid hormones are essential for normal growth
of tissues, including the nervous system. Lack of thyroid hormone during development
results in short stature and mental deficits(cretinism).
Thyroid hormone stimulates basal metabolic rate.
What are the specific actions of thyroid hormoneon body systems?
y
Cardiovascular system:Thyroid hormones increases heart
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y y
rate, cardiac contractility and cardiac output. They also
promote vasodilation, which leads to enhanced blood flow to
many organs.Central nervous system:Both decreased and increased
concentrations of thyroid hormones lead to alterations in
mental
state. Too little thyroid hormone, and the individual tends to
feel
mentally sluggish, while too much induces anxiety and
nervousness.
Reproductive system:Normal reproductive behavior and
physiology is dependent on having essentially normal levels ofthyroid hormone. Hypothyroidism in particular is commonly
associated with infertility.
f f h d h d l
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TH is critical for normal development of the skeletalsystem and musculature.
TH is also essential for normal brain development andregulates synaptogenesis, neuronal integration,
myelination and cell migration. Cretinismis a condition of severely stunted physical
and mental growth due to untreated congenitaldeficiency of thyroid hormones (congenital
hypothyroidism) due to maternal nutritional deficiencyof iodine.
Specific actions of thyroid hormone: development
Eff t t i th i d d d ti
Effects of Thyroid Hormone on Nutrient Sources
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Effects on protein synthesis and degradation:
-increased protein synthesisat low thyroid hormone levels(low metabolic rate; growth)
-increased protein degradation at high thyroid hormone levels(high metabolic rate; energy)
Effects on carbohydrates:
-low dosesof thyroid hormone increase glycogen synthesis(low metabolic rate; storage of energy)
- high dosesincrease glycogen breakdown(high metabolic rate;glucose production)
Effects on Lipids:Increased thyroid hormone levels stimulate fatmobilization, leading to increased concentrations of fatty acidsin plasma. They also enhance oxidation of fatty acids in many
tissues. Finally, plasma concentrations of cholesterol andtriglycerides are inversely correlated with TH levels.
Mechanism of Action of T3
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T3/T4 acts through the thyroid hormone receptor- intracellular, in steroid receptor superfamily
- acts as a transcription factor
- receptor binds to TRE on 5 flanking region of genes as
homodimers and/or heterodimers.- multiple forms (alphas and betas) exist
- one form (alpha-2) is an antagonist at the TRE
More on Receptor Coactivators and Corepressors
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When not bound to hormone, the thyroid hormone
receptor binds to target DNA (TRE on 5 flanking region). Itis associated with corepressor proteinsthat cause DNA to
be tightly wound and inhibit transcription.
Binding of hormone causes a conformational change,
resulting in loss of corepressor binding and association with
coactivator proteins, which loosen DNA structure and
stimulate transcription.
Expression and Regulation
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Thyroid hormone receptors are found in many tissues of
the body.
Thyroid hormone inhibits thyroid hormone receptorexpression (TRE on THR genes).
of Thyroid Hormone Receptors
One Major Target Gene of T3:
Th S di /P i ATP P
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Pumps sodium and potassium across cell membranes tomaintain resting membrane potential
Activity of the Na+/K+pump uses up energy, in the form ofATP
About 1/3rd of all ATP in the body is used by the Na+/K+ATPase
T3 increases the synthesis of Na+/K+pumps, markedlyincreasing ATP consumption.
T3 also acts on mitochondria to increase ATP synthesis
The resulting increased metabolic rate increases
thermogenesis (heat production).
The Sodium/Potassium ATPase Pump
Thyroid Hormone Deficiency: Hypothyroidism
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Early onset: delayed/incomplete physical and mental
development
Later onset (youth): Impaired physical growth
Adult onset (myxedema) : gradual changes occur.
Tiredness, lethargy, decreased metabolic rate, slowing
of mental function and motor activity, cold intolerance,
weight gain, goiter, hair loss, dry skin. Eventually
may result in coma.
Many causes (insufficient iodine, lack of thyroid gland,lack of hormone receptors, lack of TBG.)
How is Hypothyroidism Related to Goiter?
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During iodine deficiency, thyroid hormone production
decreases.
This results in increased TSH release (less negative
feedback).
TSH acts on thyroid, increasing blood flow, and
stimulating follicular cells and increasing colloid
production.
yp y
Thyroid Hormone Excess: Hyperthyroidism
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Emotional symptoms (nervousness, irritability), fatigue,
heat intolerance, elevated metabolic rate, weight loss,
tachycardia, goiter, muscle wasting, apparent bulging of
eyes, may develop congestive heart failure.
Also due to many causes (excessive TSH release,
autoimmune disorders,)
Thyroid Hormone Excess: Hyperthyroidism
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Graves' disease:A condition usually caused by
excessive production of thyroid hormone and
characterized by an enlarged thyroid gland,
protrusion of the eyeballs, a rapid heartbeat, and
nervous excitability. Also called exophthalmic
goiter.
a thioamide drug used to treat hyperthyroidism
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Regulates of Basal Metabolic Rate (BMR).
Increases oxygen consumption in most target tissues.
Permissive actions: TH increases sensitivity of target
tissues to catecholamines, thereby elevating lipolysis,
glycogenolysis, and gluconeogenesis.
a thioamide drug used to treat hyperthyroidism
GLAND THYROID
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GLAND THYROID
Terletak di leher bagian depan, di samping kiridan kanan trakea.
Kelenjar tyroid menghasilkan 3 jenis hormon :
T3 (triiodotironin)
T4 (tetraiodotironin)
Tyrokalsitonin
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Bahan dasar pembtkan hormon adalah
yodium yang diperoleh dari mknan danminuman
Fungsi kel tyroid :
Mengatur keg metabolik Merangsang oksidasi
Mengatur penggunaan O2 dan pengeluaran
CO2 Mempengaruhi perkemb susunan saraf
Merangsang pertumbuhan
GLAND PARATYROID
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GLAND PARATYROID
Menempel pada bagian anterior dan posteriorkedua lobus kelenjar tyroid, menghasilkanhormon paratiroksin.
Fungsi hormon paratyroid : Meningkatkan kadar Ca dan menurunkan kadar
fosfat
Meningkatkan resorbsi tulang shg serum Ca
meningkat Organ target PTH tulang, ginjal dan usus halus
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Parameter T3 T4
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Production rate (nmol/day) 50 110
Fraction from thyroid 0.2 1
Relative metabolic potency 1 0.3 Serum concentration Total (nmol/L) 1.8 100
Free (pmol/L) 5 20
Distribution volume (L) 40 10
Fraction intracellular 0.64 0.15
Half-life (days) 0.75 6.7