1. THYROID HORMONES
Chairperson
Dr. F.A Sattar
HOD, Dept of Psychiatry
VIMS n RC Dr. Soumya Nath Maiti
IMO

2. Overview
 Introduction
 Production, transport and conversion of thyroid
hormones
 Regulation of thyroid hormones
 Mechanism of Action and actions of thyroid
hormones
 Effect of thyroid hormone on various systems
 Hypo and hyperthyroidism
 Summary

3. Introduction - Thyroid Gland
 The thyroid gland, located immediately
below the larynx on each side of and anterior
to trachea, is one of the largest of endocrine
glands.
 It secretes two major hormonesThyroxine
and triidothyronine.
 It also secretes calcitonin, an important
hormone for calcium meatabolism

5. Introduction - Thyroid Hormones
 There are two biologically active thyroid hormones:
- tetraiodothyronine (T4; usually called thyroxine)
- triiodothyronine (T3)
 Derived from modification of tyrosine.

6. Differences between T4 and T3
 The thyroid secretes about 80 microg ofT4, but only
5 microg ofT3 per day.
 However,T3 has a much greater biological activity
(about 10 X) thanT4.
T4
thyroid
I-
T3

7. Importance of Iodine
• Thyroid hormones are unique biological
molecules in that they incorporate iodine in their
structure.
• Thus, adequate iodine intake (diet, water) is
required for normal thyroid hormone production.
• Major sources of iodine:
- iodized salt
- iodated bread
- dairy products
- shellfish
• Minimum requirement: 75 micrograms/day

8. Iodine Metabolism
• Dietary iodine is absorbed in the GI tract, then
taken up by the thyroid gland.The basal
membrane of the thyroid cell has the specific
ability to pump iodine actively to the interior of
the cell.This is called iodide trapping.
• Iodide taken up by the thyroid gland is oxidized
by peroxide in the lumen of the follicle:
peroxidas
eI- I+
• Oxidized iodine can then be used in production of
thyroid hormones.

9. Production of Thyroglobulin
 Pituitary producesTSH, which binds to follicle
cell receptors.
 The follicle cells of the thyroid produce
thyroglobulin.
 Thyroglobulin is released into the colloid
space, where it’s tyrosine residues are iodinated
by I+.
 This results in tyrosine residues which have one
or two iodines attached (monoiodotyrosine or
diiodotyrosine).

10. More and more of iodotyrosine residues
become coupled with one another. The major
production of this coupling reaction is
thyroxine molecule.
One molecule of monoiodotyrosine couples
with diidotyrosine to form tridotyrosine
(T3).

11. Transport of Thyroid Hormones
• Thyroid hormones are not very soluble in water (but are
lipid-soluble).
• Thus, they are found in the circulation associated with
binding proteins:
-Thyroid Hormone-Binding Globulin (~70% of hormone)
- Pre-albumin (transthyretin), (~15%)
-Albumin (~15%)
• Less than 1% of thyroid hormone is found free in the
circulation.
• Only free and albumin-bound thyroid hormone is
biologically available to tissues.

12. Conversion of T4 to T3
 T3 has much greater biological activity thanT4.
 A large amount ofT4 (25%) is converted toT3 in
peripheral tissues.
 This conversion takes place mainly in the liver and
kidneys. TheT3 formed is then released to the blood
stream.
 In addition toT3, an equal amount of “reverseT3”
may also be formed. This has no biological activity.

13.  The thyroid gland is capable of storing many
weeks worth of thyroid hormone (coupled to
thyroglobulin).
 If no iodine is available for this period, thyroid
hormone secretion will be maintained.
Storage of thyroglobulin

14. Regulation of Thyroid Hormone
Levels
 Thyroid hormone synthesis and secretion is
regulated by two main mechanisms:
- an “autoregulation” mechanism, which
reflects the available levels of iodine
- Neuroendocrine regulation by the
hypothalamus and anterior pituitary

15. Autoregulation of Thyroid Hormone
Production
 The rate of iodine uptake and incorporation into
thyroglobulin is influenced by the amount of
iodide available:
- low iodide levels increase iodine transport into
follicular cells
- high iodide levels decrease iodine transport into
follicular cells
Thus, there is negative feedback regulation of
iodide transport by iodide.

16. Neuroendocrine Regulation of
Thyroid Hormones: Role of TSH
 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 and biological activity

17. Action of TSH on the Thyroid
 TSH acts on follicular cells of the thyroid.
- increases iodide transport into follicular cells
- increases production and iodination of
thyroglobulin
- increases endocytosis of colloid from lumen into
follicular cells
Na+
I-
thyroglobulinfollicle
cell
gene
I-
endocytosis
thyroglobulin
T3 T4
colloid droplet
I-I+
iodination
thyroglobulin
Na+ K+
ATP

18. Regulation of TSH Release from
the Anterior Pituitary
 TSH release is influenced by hypothalamicTRH, and
by thyroid hormones themselves.
 Thyroid hormones exert negative feedback onTSH
release at the level of the anterior pituitary.
- inhibition ofTSH synthesis
- decrease in pituitary receptors forTRH
hypothalamus
TRH
TRH receptor
TSH synthesis
pituitary T3/T4
+
-
-

19. Influence of TRH on TSH Release
• Thyrotropin-releasing hormone (TRH) is a
hypothalamic releasing factor which travels through
the pituitary portal system to act on anterior
pituitary thyrotroph cells.
TRH phospholipase C
G protein-coupled
receptor
IP3 calcium
DAG PKC
calmodulin
• Thyroid hormones also inhibit TRH synthesis.

20. Negative Feedback Actions of
Thyroid Hormones on TSH Synthesis
and Release
hypothalamus
TRH
TRH receptor
TSH synthesis
pituitary
T3/T4
+
-
-
-
TRH synthesis
Thyroid gland
follicle cell receptors
TSH binds

21. Other Factors Regulating Thyroid
Hormone Levels
 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: increasesT3 levels in other
animals, but not in humans.
 Any condition that increases body energy
requirements (e.g., pregnancy, prolonged cold)
stimulates hypothalamus TRH TSH (Pit)

22. Mechanism of Action of Thyroid
hormones
 The general effect of thyroid hormone is to
activate nuclear transcrpition of large numbers
of genes.
 Therefore in virtually all cells of the body, great
numbers of protein enzymes, structural
proteins, transport proteins are synthesized.
 The net result is generalized increase in
functional activity throughout the body.

23. T3/T4 acts through the thyroid hormone
receptor, which are attached to the DNA.
When not bound to hormone, the thyroid
hormone receptor binds to target DNA. It
is associated with corepressor proteins
that 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.

24. One Major Target Gene of T3: The
Na+/K+ ATPase Pump
 Pumps sodium and potassium across cell
membranes to maintain resting membrane potential
 Activity of the Na+/K+ pump uses up energy, in the
form of ATP
 About 1/3rd of all ATP in the body is used by the
Na+/K+ ATPase
 T3 increases the synthesis of Na+/K+
pumps, markedly increasing ATP consumption.
 T3 also acts on mitochondria to increase ATP
synthesis
 The resulting increased metabolic rate increases
thermogenesis (heat production).

25. Actions of Thyroid Hormones
 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.

26. Effects of Thyroid Hormone on
Nutrient Sources
• Effects on protein synthesis and degradation:
-increased protein synthesis at low thyroid
hormone levels (low metabolic rate; growth)
-increased protein degradation at high thyroid
hormone levels (high metabolic rate; energy)
• Effects on carbohydrates:
-low doses of thyroid hormone increase glycogen
synthesis (low metabolic rate; storage of energy)
- high doses increase glycogen breakdown (high
metabolic rate; glucose production)

27. Thyroid Hormone Actions
which Increase Oxygen
Consumption
 Increase mitochondrial size, number and key
enzymes
 Increase plasma membrane Na-K ATPase
activity
 Increase futile thermogenic energy cycles
 Decrease superoxide dismutase activity

28. Effects of Thyroid Hormones
on the Cardiovascular System
 Increase heart rate
 Increase force of cardiac contractions
 Increase stroke volume
 Increase Cardiac output
 Up-regulate catecholamine receptors

29. Effects of Thyroid Hormones
on the Respiratory System
 Increase resting respiratory rate
 Increase minute ventilation
 Increase ventilatory response to hypercapnia
and hypoxia

30. Effects of Thyroid Hormones
on the Renal System
 Increase blood flow
 Increase glomerular filtration rate

31. Effects of Thyroid Hormones
on Oxygen-Carrying Capacity
 Increase RBC mass
 Increase oxygen dissociation from
hemoglobin

32. Effects of Thyroid Hormones
on Intermediary Metabolism
 Increase glucose absorption from the GI tract
 Increase carbohydrate, lipid and protein
turnover
 Down-regulate insulin receptors
 Increase substrate availability

33. Effect of Thyroid Hormone on growth
 Required for GH and prolactin production and
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. Increased heat
production (calorigenic effect)

34. Effects Thyroid Hormones in
Growth and Tissue
Development
 Increase growth and maturation of bone
 Increase tooth development and eruption
 Increase growth and maturation of
epidermis,hair follicles and nails
 Increase rate and force of skeletal muscle
contraction
 Inhibits synthesis and increases degradation of
mucopolysaccharides in subcutaneous tissue

35. Effects of Thyroid Hormones
on the Nervous System
 Critical for normal CNS neuronal
development
 Enhances wakefulness and alertness
 Enhances memory and learning capacity
 Required for normal emotional tone
 Increase speed and amplitude of peripheral
nerve reflexes

36. Effects of Thyroid Hormones
on the Reproductive System
 Required for normal follicular development
and ovulation in the female
 Required for the normal maintenance of
pregnancy
 Required for normal spermatogenesis in the
male

37. Thyroid Hormone Deficiency:
Hypothyroidism
 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 ofTH
binding globulin)

38. Hypothyroidism and Goiter
 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.

39. Thyroid Hormone Excess:
Hyperthyroidism
 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 (excessiveTSH
release, autoimmune disorders,)

41. Cretinism
 Cretinism is caused by extreme
hypothyroidism during fetal life, infancy, or
childhood. Commonly due to Congenital lack
of thyroid gland or failure of gland to produce
hormone due to genetic defect.
 This condition Is characterized by failure of
body growth and mental retardation

42.  A neonate without a thyroid gland may have
normal appearance as it was supplied with
thyroid hormones by the mother in utero.
 But within a few weeks neonates movements
become sluggish and growth begin to be
greatly retarded.
 Treatment with adequate iodine or thyroxine
usually causes return to normal growth. But
unless it is treated within a few weeks after
birth mental retardation becomes
permanent.

43. Thyroid hormones:
Key Points
• Held in storage
• Bound to mitochondria, thereby increasing ATP
production
• Bound to receptors activating genes that control
energy utilization
• Exert a calorigenic effect

44. References
 Textbook of Medical Physiology 11th edition
by GUYTON & HALL
 Principals of Pharmacology by BENNET &
BROWN.

45. Thank
You