Hormones ( Thyroid Hormone )

Hormones ( Thyroid Hormone )

1. 1

Hormones
• Hormones: are the chemical messengers of our system that coordinates the
communication between cells and tissues, thus maintaining the overall homeostasis
of the body
• Hormone: A molecule released by a cell or a gland in one part of the body that
sends out messages affecting cells in other parts of the organism
The major glands that make up the human endocrine system include the: ♦
- Hypothalamus. - Pituitary glands. - Thyroid. - Parathyroid.
Adrenal glands. - Pancreas.- - Pineal body.
Reproductive glands (which include the ovaries and testes)-








Mechanism of Hormone action

2. 2

steroid Hormones)-(Non Fixed membrane receptor mechanism: ◘
Growth in compositions such as aminesor proteinThe hormones that are •
etc shows this TSH, FSH, Adrenaline, Insulin, oxytocin, ADH, hormone
mechanism of action.
and cannot passes through the lipid membrane water solubleThese hormones are •
and they have their target receptor on the cell membrane.
• The receptor are fixed on the cell membrane, so hormone can bind on the specific
receptor.
• Binding of hormone on specific receptor on target cell activates the enzyme
Adenylcyclase in the cell membrane and causes production of cyclic AMP (cAMP).
• cAMP act as secondary messenger.
- It diffuse through the cell membrane and activates (Protein Kinase) various
enzymatic reaction to cause biochemical changes.
- After the target cell responded to the changes, cAMP is deactivated by a group of
enzyme Phosphodiesterase

Figure: Fixed membrane receptor mechanism of hormone action ( Eg. FSH)

3. 3

hormones)(steroid :Mobile receptor mechanism ◘
hormones Fatty acids and steroid hormoneshormones such as lipid solubleThe •
can easily passes through the plasma membrane.
• They have their receptor inside the cell, freely floating in the cytoplasm.
• Binding of hormone to the specific receptor activates the enzymatic activity of the
cell for biochemical changes.
• Some hormones (testosterone, progesterone, estrogen, cortisol, thyroxine)
have their receptor localized inside the nucleus, the hormone-receptor complex are
carried inside the nucleus.
• The hormone-receptor complex initiates transcription of the DNA to form specific
mRNA.
• mRNA initiate protein synthesis in the cytoplasm.
• The protein (enzyme) causes biochemical changes in the cell.











Figure: Mobile receptor mechanism of hormone action (Estrogen)

4. 4

◘ Thyroid Hormone:
• Thyroid Hormones are amine hormones and so their
synthesis is based on the amino acid tyrosine.
• The primary synthetic organ of Thyroid Hormones is
the thyroid gland which produces about twenty times
more T4 compared to T3.

• T4 is then converted to either T3 or rT3 by the enzyme 'Iodinase' which is present
throughout the body's tissues.
the basic units of thyroid which are thyroid folliclesThe thyroid gland is full of •
. hormone synthesis
• The thyroid follicles are surrounded by a lining of follicular epithelial cells and
Thyroid thef proteinacious material termed contain an acellular lumen full o
. Colloid
• Synthesis of thyroid hormones is a complex multi-step process which possesses
steps that occur within the follicular epithelial cells and also within the acellular
follicular lumen.

5. 5

♦ Thyroid Hormone Synthesis: *
♣ Iodine Transport
• Large amounts of Iodine are required for synthesis of physiological levels of
thyroid hormones.
• To generate sufficient concentrations of Iodine, the ionic form of the atom, Iodide
(I
-
) is actively transported from the blood stream into the follicular lumen by the
Follicular Epithelial Cells.
• Consequently, Iodide is highly concentrated in the thyroid gland compared to the
rest of the body.
♣ Thyroglobulin Synthesis
• Thyroglobulin is a protein that contains large numbers of tyrosine amino acids
that go on to become individual thyroid hormone molecules.
• Thyroglobulin is synthesized within the follicular epithelial cell and secreted into
the follicular lumen.

6. 6

♣ Thyroid Peroxidase

• Thyroid Peroxidase is an enzyme present in the acellular colloid of the follicular
lumen and performs several key reactions.
• Thyroid Peroxidase first generates I2 by oxidizing I
-
ions present in the follicular
lumen.
• Thyroid Peroxidase then "organifies" the generated I2 by covalently linking it
with the tyrosine residues present in Thyroglobulin.
• This generates either single or doubly-iodinated species of tyrosine, termed
"Monoiodotyrosine (MIT)" and "Diiodotyrosine (DIT)", respectively
• Peroxidase then combines MIT and DIT residues to generate T4 or T3 species
within the thyroglobulin protein, a process termed "Coupling".
• T4 is generated by combining two DIT residues while T3 is generated by
combining one DIT residue with one MIT residue.
• Importantly, peroxidase is much more efficient at combining of two DIT residues
and thus generation of T4 occurs much more readily, explaining why the thyroid
gland primarily produces T4 rather than T3.
• Notably, some MIT and DIT residues do not get coupled and so peroxidase-
processed thyroglobulin will retain some MIT and DIT residues.
Endocytosis of Peroxidase-processed Thyroglobulin ○
• Peroxidase-processed thyroglobulin is then endocytosed by follicular epithelial
cells on a regulated basis whenever the thyroid gland is stimulated to release
thyroid hormone into the circulation.
• Importantly, peroxidase-processed thyroglobulin within the follicle can act as a
reservoir for thyroid hormones in the absence of stimulation for hormone release.
• Importantly, this reservoir of peroxidase-processed thyroglobulin is usually
enough for months of use explaining why defects in thyroid hormone synthesis
often take months to become clinically apparent.

7. 7

○ Release of T4 and T3 from Thyroglobulin
• Once endocytosed into the follicular epithelial Cell, the Thyroglobulin is broken
down by lysosomes, thus releasing attached T4, T3, MIT, and DIT.
• T4 and T3 are then transported out of the follicular epithelial cells and into the
circulation.
• The iodine atoms of MIT and DIT are salvaged and transported back into the
follicular lumen as I
-
.

https://www.youtube.com/watch?v=b7JFqGMi9pk: YouTubeWatch on
♦ Thyroid Hormone Regulation of Metabolism
• Local activation of thyroxine (T4), to the active form, triiodothyronine (T3),
by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of
metabolism.
• D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT),
and skeletal muscle and is required for adaptive thermogenesis.
• The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and
thyroid stimulating hormone (TSH).

8. 8

• In addition to TRH/TSH regulation by TH feedback, there is central modulation by
nutritional signals, such as leptin, as well as peptides regulating appetite.

• The nutrient status of the cell provides feedback on TH signaling pathways through epigentic
modification of histones.
nervous system occurs signaling with the adrenergic Thyroid hormone)( Integration of TH•
, but also centrally, in the )brown adipose tissue( peripherally, in liver, white fat, and BAT
hypothalamus.
regulates cholesterol and carbohydrate metabolism through )(The thyroid hormone receptor TR•
direct actions on gene expression as well as cross-talk with other nuclear receptors, including
peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid
signaling pathways.
• TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic
gluconeogenesis.
• The role of TH in regulating metabolic pathways has led to several new therapeutic targets
for metabolic disorders.
• Understanding the mechanisms and interactions of the various TH signaling pathways in
metabolism will improve our likelihood of identifying effective and selective targets.

9. 9

Functions of Thyroid hormone ♦
• The thyroid hormones increase the metabolic activities of almost all the tissues of
the body.
• The Basal Metabolic Rate (BMR) is increased.
expended while at rest. energy ) is the rate ofBMR( metabolic rateBasal
• The rate of utilization of foods for energy is greatly accelerated.
• Although the rate of protein synthesis is increased, at the same time the rate of
protein catabolism is also increased.
• The growth rate of young people is greatly accelerated.
• The mental processes are excited, and the activities of most of the other
endocrine glands are increased.
• mitochondria in most cells of the increase in size as well as number
- the total membrane surface area of the mitochondria increases
– more ATP
• ↑ Na
+
K
+
ATPase activity
- ↑ transport of both sodium and potassium ions through the cell membranes
– more energy
– more heat
Growth
- the effect of thyroid hormone on growth is manifest mainly in growing children.
• In those who are hypothyroid, the rate of growth is greatly retarded.
• In those who are hyperthyroid, excessive skeletal growth often occurs, causing
the child to become considerably taller at an earlier age
- amphibian metamorphosis
• To promote growth and development of the brain during fetal life and for the
first few years of postnatal life
– mental retardation

10. 10

:Metabolic Functions ♦
Fat Metabolism
- lipids are mobilized rapidly from the
fat tissue, which ↓ the fat stores of the
body.
- Also ↑ the free fatty acid
concentration in the plasma and ↑ the
oxidation of free fatty acids by the
cells
• ↑ thyroid hormone
- ↓ the concentrations of cholesterol
(secretion in the bile and loss in the
feces), phospholipids, and triglycerides
in the plasma, it ↑ the free fatty acids.
• ↓ thyroid secretion
- ↑ the plasma concentrations of
cholesterol, phospholipids, and
triglycerides & causes excessive
deposition of fat in the liver
- atherosclerosis
Carbohydrate Metabolism
- Rapid uptake of glucose by the cells,
↑ glycolysis,
↑ gluconeogenesis,
↑ rate of absorption from the GIT, and
↑ insulin secretion



Nerve, Muscle, Sleep
• CNS (Central Nervous System)
– excitation
- extreme nervousness
- anxiety complexes
- extreme worry
– paranoia
– restless
– Reaction time
Muscle
- stamina, strength ↑
- long term weak due to protein
catabolism
– vice versa sluggish, relax slowly
• Hyperthyroidism
– Fine (not coarse) muscle tremor
- tremor can be observe by placing a
sheet of paper on the extended fingers
and noting the degree of vibration of
the paper

Metabolic, CVS
• Thyroid hormone ↑ the quantities of
many bodily enzymes and because
vitamins are essential parts of some of
the enzymes or coenzymes, thyroid
hormone causes ↑ need for vitamins
– deficiency
• ↑ thyroid hormone
basal metabolic rate)(↑ BMR -
- ↓ body weight
–↑ appetite
CVS (cardiovascular system)
– ↑ metabolism in the tissues causes more
rapid utilization of oxygen & release of
greater quantities of metabolic end products
– vasodilation
- ↑ blood flow.
• blood flow ↑ in the skin for heat
elimination
• ↑ blood flow
- ↑ cardiac output

11. 11

Sleep

- the hyperthyroid subject often has a
feeling of constant tiredness, but
because of the excitable effects of
thyroid hormone on the synapses, it is
difficult to sleep
• extreme somnolence is characteristic
of hypothyroidism, with sleep
sometimes lasting 12 to 14 hours a day
Endocrine, Sexual

Endocrine
- ↑ need of insulin, PTH,
glucocorticoids
- Relation to Catecholamines

CVS, RS, GIT

• ↑ in HR (heart rate)
– resting tachycardia
• ↑ in heart strength
– long term failure due to ↑ in CO
unchanged Arterial Pressure)Mean ( • MAP
Diastolic ( ↓ ↑, DBP (Systolic Blood Pressure) SBP –
blood pressure)
↑ pulse pressure)( PP -

• RS (respiration rate)
- ↑ the rate and depth of respiration

• GIT (Gastrointestinal Track)
- ↑ appetite and food intake
- ↑ secretion of the digestive juices
- ↑ GIT motility
– diarrhea & constipation

Sexual Function

• In men, lack of thyroid
hormone is likely to cause loss of
libido
- great excesses of the hormone,
sometimes cause impotence

• In women, lack of thyroid
hormone often causes
menorrhagia, polymenorrhea,
irregular periods, amenorrhea,
decreased libido
- hyperthyroid woman,
oligomenorrhea, amenorrhea
• Milk secretion is decreased in
hypothyroidism and stimulated by
thyroid hormones

12. 12

Obesity and thyroid function
• the alterations of thyroid hormones in obesity suggest an adaptation process.
• Since rapid weight loss is associated with a decrease of TSH and T3, the
resulting decrease in resting energy expenditure (REE) may contribute towards
the difficulties maintaining weight loss.
• Leptin seems to be a promising link between obesity and alterations of
thyroid hormones since leptin concentrations influence TSH release.
Thyroid Hormone and Carbohydrate Metabolism
• Thyrotoxicosis can alter carbohydrate metabolism in a type 2 diabetic
patient to such an extent that diabetic ketoacidosis develops if untreated.
• Based on the current understanding of this relationship, all diabetic patients
should be screened for thyroid dysfunction because correcting hyperthyroidism
can profoundly affect glucose homeostasis.
• Similarly, patients presenting in diabetic ketoacidosis should undergo a thyroid
function assessment.
Anti thyroid Substances
Thiocyanate Ions Decrease Iodide Trapping
• The same active pump that transports iodide ions into the thyroid cells can
also pump thiocyanate ions, perchlorate ions, and nitrate ions
- competitive inhibition
Pituitary via negative feedback
– enlarged thyroid gland
– goiter
• Propylthiouracil
↓ Thyroid Hormone Formation
• Propylthiouracil, methimazole
and carbimazole
- block the peroxidase enzyme that is
required for iodination of tyrosine
- block the coupling of two iodinated
tyrosines -

• ↓ T3, T4
- ↑ TSH from Ant.

13. 13

ص نم31 ل02 مهنع اوبتكا تلاق هروتكدلا تادايز ,, اوبيجت نكممو تنرتنلاا نم هتبج يللا اوركاذت نكمم
مكسفنب متنا .

14. 14

Hypothyroidism: ◘
• Hypothyroidism is a common endocrine disorder resulting from deficiency of
thyroid hormone.
• it is understandable that people with this condition will have symptoms associated
with a slow metabolism.
Causes of Hypothyroidism
• There are two fairly common causes of hypothyroidism.
- The first is an inflammation of the thyroid gland, which leaves a large percentage
of the cells of the thyroid damaged (or dead) and incapable of producing sufficient
hormone.
- The most common cause of thyroid gland failure is called autoimmune
thyroiditis (also called Hashimoto's thyroiditis), a form of thyroid inflammation
caused by the patient's own immune system.

- The second major cause is the broad category of "medical treatments."

Symptoms of Hypothyroidism
 Fatigue
 Weakness
 Weight gain or increased difficulty losing weight
 Coarse, dry hair
 Dry, rough pale skin
 Hair loss
 Cold intolerance (you can't tolerate cold temperatures like those around you)
 Muscle cramps and frequent muscle aches
 Constipation
 Depression
 Irritability
 Memory loss
 Abnormal menstrual cycles
 Reduced Heart rate

15. 15

◘ Hyperthyroidism:
• Hyperthyroidism occurs when the thyroid makes too much T4, T3, or both.
• People with this condition will have symptoms associated with an increase in
metabolism.

Causes of Hyperthyroidism

• Graves' disease, an autoimmune disorder, is the most common cause of
hyperthyroidism.
Other causes of hyperthyroidism include:
- excess iodine, a key ingredient in T4 and T3
- thyroiditis, or inflammation of the thyroid, which causes T4 and T3 to leak out of
the gland
- tumors of the ovaries or testes
- benign tumors of the thyroid or pituitary gland
- large amounts of tetraiodothyronine taken through dietary supplements or
medication
Symptoms of hyperthyroidism include:
appetite increased•
• nervousness
• restlessness
concentrate to inability•
weakness•
heartbeat irregular•
sleeping difficulty•
• fine, brittle hair
itching•
loss hair•
vomiting and nausea•
dizziness•
breath of shortness•
consciousness of loss•
• fast, irregular heart rate

16. 16

◘ Thyrotropin-releasing
hormone (TRH)
• Also called thyrotropin-releasing
factor (TRF) or thyroliberin, is
a releasing hormone, produced by
the hypothalamus, that stimulates the
release of thyrotropin (thyroid-
stimulating hormone or TSH)
and prolactin from the anterior
pituitary.
• It controls thyroid hormone production
and also has several other important roles
in the body.
• Thyrotropin-releasing hormone is the master regulator of thyroid gland growth
and function (including the secretion of the thyroid
hormones thyroxine and triiodothyronine).
• These hormones control the body’s metabolic rate, heat generation,
neuromuscular function and heart rate, among other things.
• If there is insufficient thyroid hormone available for the brain, this will be
detected by the hypothalamus and thyrotropin-releasing hormone will be released
into the blood supplying the pituitary gland.
• The effect of thyrotropin-releasing hormone on the pituitary gland is to trigger
thyroid stimulating hormone release, which, in turn stimulates the thyroid gland to
make more thyroid hormone.
• In summary, thyrotropin-releasing hormone is the brain’s first messenger signal in
the many actions controlling thyroid hormone secretions.
• If a person has too little thyrotropin-releasing hormone, they will develop thyroid
underactivity (hypothyroidism)
. This is a rare condition, usually due to an injury or tumor which destroys this area
of the hypothalamus.

17. 17

stimulating hormone (TSH):-Thyroid ◘
(also known stimulating hormone-Thyroid•
for hTSH , orTSH ,thyrotropic hormone ,thyrotropin as
that stimulates pituitary hormone TSH) is ahuman
), and 4(T thyroxine gland to produce thyroid the
) which stimulates the metabolism of 3(T triiodothyronine then
almost every tissue in the body.
), which is the active hormone that 3(T triiodothyronine is converted to 4T -
stimulates metabolism. About 80% of this conversion is in the liver and other
organs, and 20% in the thyroid itself.
TSH is secreted throughout life but particularly reaches high levels during the •
periods of rapid growth and development, as well as in response to stress.
releasing -thyrotropin he base of the brain, produces, in thypothalamus The•
to produce TSH. dpituitary glan (TRH). TRH stimulates the hormone
is also produced by the hypothalamus, and has an opposite effect on Somatostatin•
the pituitary production of TSH, decreasing or inhibiting its release.
) in the blood regulates the 4and T 3thyroid hormones (TThe concentration of •
concentrations are low, the production of 4and T 3pituitary release of TSH; when T
gh, TSH concentrations are hi 4and T 3TSH is increased, and, conversely, when T
loop. negative feedback is an example of a Thisproduction is decreased;
◘ Thyroxine
• Thyroxine is the main hormone secreted into the bloodstream by the thyroid
gland.
• It is the inactive form and most of it is converted to an active form
called triiodothyronine by organs such as the liver
and kidneys.
• Thyroid hormones play vital roles in regulating the
body’s metabolic rate, heart and digestive functions,
muscle control, brain development and maintenance
of bones.

18. 18

How is thyroxine controlled?
• The production and release of thyroid hormones, thyroxine and triiodothyronine,
is controlled by a feedback loop system that involves the hypothalamus in the brain
and the pituitary and thyroid glands.
• The hypothalamus secretes thyrotropin-releasing hormone which, in turn,
stimulates the pituitary gland to produce thyroid stimulating hormone.
• This hormone stimulates the production of the thyroid hormones, thyroxine and
triiodothyronine, by the thyroid gland.
• This hormone production system is regulated by a feedback loop so that when the
levels of the thyroid hormones (thyroxine and triiodothyronine) increase, they
prevent the release of both thyrotropin-releasing hormone and thyroid stimulating
hormone.
• This system allows the body to maintain a constant level of thyroid hormones in
the body.
What happens if I have too much thyroxine?
• The release of too much thyroxine in the bloodstream is known as thyrotoxicosis.
• This may be caused by overactivity of the thyroid gland (hyperthyroidism), as
in Graves' disease, inflammation of the thyroid or a benigntumour.
• Thyrotoxicosis can be recognised by a goitre, which is a swelling of the neck due
to enlargement of the thyroid gland.
• Other symptoms of thyrotoxicosis include intolerance to heat, weight loss,
increased appetite, increased bowel movements, irregular menstrual cycle, rapid or
irregular heartbeat, palpitations, tiredness, irritability, tremor, hair thinning/loss and
retraction of the eyelids resulting in a ‘staring’ appearance.
What happens if I have too little thyroxine?
• Too little production of thyroxine by the thyroid gland is known
as hypothyroidism.
• It may be caused by autoimmune diseases, poor iodine intake or caused by the use
of certain drugs. Sometimes, the cause is unknown.

19. 19

• Thyroid hormones are essential for physical and mental development so
untreated hypothyroidism before birth or during childhood can cause mental
impairment and reduced growth.
• Hypothyroidism in adults causes reduced metabolism.
• It can result in symptoms such as fatigue, intolerance of cold temperatures, low
heart rate, weight gain, reduced appetite, poor memory, depression, stiffness of the
muscles and reduced fertility.
◘ Triiodothyronine (T3)
.thyroxine hormone, thyroid thethyronine is the active form of Triiodo•
Approximately 20% of triiodothyronine is secreted into the bloodstream directly •
.thyroid gland by the
The remaining 80% is produced from conversion of thyroxine by organs such as •
. kidneys the liver and
, heart metabolic rate vital roles in regulating the body’sThyroid hormones play •
and digestive functions, muscle control, brain development and function, and the
maintenance of bones.
How is triiodothyronine controlled?
• The production and release of thyroid hormones, thyroxine and triiodothyronine,
is controlled by a feedback loop involving the hypothalamus, pituitary gland and
thyroid gland.
• Activation of thyroid hormones is then controlled in body tissues such as the liver,
brain and kidneys by enzymes called deiodinases which convert thyroxine into the
active form triiodothyronine.
• Most of the body’s circulating triiodothyronine (about 80%) is produced in this
way.
• The thyroid hormone production system is regulated by a feedback loop so that
when the levels of the thyroid hormones thyroxine and triiodothyronine increase,
they prevent the release of both thyrotropin-releasing hormone from the
hypothalamus and thyroid stimulating hormone from the pituitary gland.
• This system allows the body to maintain a constant level of thyroid hormones in
the body.

20. 20

What happens if I have too much triiodothyronine?
• Thyrotoxicosis is the name of the condition in which people have too much
thyroid hormone in their bloodstreams.
• It may result from overactivity of the thyroid gland (hyperthyroidism) from
conditions such as Graves' disease, inflammation of the thyroid or
a benign tumour.
• Thyrotoxicosis may be recognised by a goitre, which is a swelling of the neck due
to enlargement of the thyroid.
• Other symptoms of thyrotoxicosis include heat intolerance, weight loss, increased
appetite, increased bowel movements, irregular menstrual cycle, rapid or irregular
heartbeat, palpitations, tiredness, irritability, tremor, hair thinning/loss and
retraction of the eyelids, which results in a ‘staring’ appearance.
What happens if I have too little triiodothyronine?
• Hypothyroidism is the term for the production of too little thyroid hormone by the
thyroid gland.
• This may be because of autoimmune diseases (such as Hashimoto’s disease), very
poor iodine intake or due to some medications.
• Since thyroid hormones are essential for physical and mental development,
untreated hypothyroidism before birth and during childhood can result in learning
disability and reduced growth.
• Hypothyroidism in adults results in a slowing of the body’s functions with
symptoms such as tiredness, intolerance to cold temperatures, low heart rate, weight
gain, reduced appetite, poor memory, depression, stiffness of the muscles and
reduced fertility.