Salient Features of India constitution especially power and functions
Thyroid Hormone
1. THYROID HORMONE:
• Gross and Microscopic Anatomy of the Thyroid Gland.
• Production of Thyroid Hormones.
• Transport of T3 and T4
• Actions of Thyroid Hormones.
• Regulation of Thyroid Hormones.
• Hyper- and Hypothyroidism
PREPARED BY:
Dr.Abdul Wahab Aslam
2. HIsTOlOgY Of THE THYROID glaND
• The thyroid gland contains numerous follicles, composed of
epithelial follicle cells and colloid.
Also, between follicles are Para-follicular cells, which produce
Calcitonin.
3. THE THYROID glaND – HIsTOlOgY:
Squamous epithelial cells, cuboidal cells (follicle cells).
Gland is composed of hollow spheres, called colloid follicles.
Colloid fills the follicle cavities.
Follicle cells produce thyroglobulin.
I
7. THYROID HORMONEs:
There are two biologically active thyroid hormones:
- Tetraiodothyronine(T4; usually called thyroxine)
- Triiodothyronine (T3)
Derived from modification of tyrosine(amino acid).
8. DIffERENcEs bETwEEN T4 aND T3:
• The thyroid secretes about 80mg of T4, but only 5mg of T3 per
day.
• However, T3 has a much greater biological activity about 10
folds than T4.
• An additional 25mg/day of T3 is produced by peripheral
monodeiodination of T4 by enzyme called 5’ Monodeiodenase.
thyroid
T4 T3
I-
9. MajOR sOuRcEs Of IODINE:
• Thyroid hormones are unique biological molecules in that they
incorporate iodine in their structure.
• Thus, adequate iodine intake either through diet or water is
required for normal thyroid hormone production.
• Major sources of iodine are:
- iodized salt
- iodated bread
- dairy products
- shellfish
• Minimum requirement(RDA): 75 micrograms/day
• US intake: 200 - 500 micrograms/day
10. IODINE METabOlIsM
• Dietary iodine is absorbed in the GI tract, then taken up by the
thyroid gland (or removed from the body by the kidneys).
• About 80% of the iodine is lost in urine where as only 20 % is
taken up by the Thyroid follicular cells.
• The transport of iodide into follicular cells is dependent upon a
Na+/I- co-transport system.
• Iodide taken up by the thyroid gland is oxidized by peroxide in
the lumen of the follicle:
Peroxidase
I -
I+
• Oxidized iodine can then be used in production of thyroid
hormones.
11. THE NExT sTEp: pRODucTION Of THYROglObulIN:
Pituitary produces TSH, which binds to follicle cell receptors.
The follicle cells of the thyroid produce thyroglobulin.
Thyroglobulin is a very large glycoprotein.
Thyroglobulin is released into the colloid space, where it’s
tyrosine residues are iodinated by I+.
This results in formation of monoiodotyrosine or diiodotyrosine.
15. TRANSpORT Of ThyROId hORmONES
• Thyroid hormones are lipid-soluble.
• Thus, they are found in the circulation associated with binding
proteins:
- Thyroid Hormone-Binding Globulin(TBG) (~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.
• Among the amount of thyroid hormone production and release
T4 is approximately 95% and T3 is 5%. But biological active is
T3 so T4 is converted to T3 in peripheral tissues by the enzyme
5’monodeiodinase and become active.
16. CONvERSION Of T4 TO T3
T3 has much greater biological activity than T4.
A large amount of T4 (25%) is converted to T3 in peripheral
tissues.
This conversion takes place mainly in the liver and kidneys. The
T3 formed is then released to the blood stream.
In addition to T3, an equal amount of “Reverse T3” may also be
formed. This has no biological activity.
T3 MIT + DIT
Reverse T3 DIT + MIT
17. REGULATION Of ThyROId hORmONE LEvELS:
• Thyroid hormone synthesis and secretion is regulated by two
main mechanisms:
- An “auto regulation” mechanism, which reflects the
available levels of iodine.
- Regulation by the hypothalamus and anterior pituitary.
18. AUTO REGULATION 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.
19. 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, hCG)
- TSH beta subunit, which gives specificity of receptor binding and
biological activity.
20. 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+ K+ I- Na+
gene
ATP
follicle colloid droplet thyroglobulin I-
cell
endocytosis
thyroglobulin thyroglobulin
iodination I+ I-
T3 T4
21. mEChANISm Of ACTION Of TSh
• TSH binds to G protein-coupled receptor on thyroid follicular
cells.
• Specifically, it activates a Gs-coupled receptor which leads to
activation of Adenyl cyclase resulting in increased c-AMP
production and PKA (Protein Kinase-A) activation.
Adenylyl
TSH Cyclase
Gsa
ATP cyclic AMP
Follicle cell
Protein kinase
A
22. REGULATION Of TSh RELEASE fROm
ThE ANTERIOR pITUITARy
• TSH release is influenced by hypothalamic TRH, and by thyroid
hormones themselves.
• Thyroid hormones exert negative feedback on TSH release at
the level of the anterior pituitary.
- inhibition of TSH synthesis
- decrease in pituitary receptors for TRH
hypothalamus
+ TRH
TRH receptor
-
-
pituitary
TSH synthesis
T3/T4
23. 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 acts through G protein-coupled receptors, activating the IP3
(Ca2+) and DAG (PKC) pathways to cause increased production
and release of TSH.
IP3 calcium
G protein-coupled
receptor
TRH phospholipase C calmodulin
DAG PKC
• Thyroid hormones also inhibit TRH synthesis.
24. NEGATIvE fEEdbACk ACTIONS Of ThyROId
hORmONES ON TSh SyNThESIS ANd RELEASE
TRH synthesis
hypothalamus
+ TRH -
TRH receptor -
T3/T4
pituitary
-
TSH synthesis
TSH binds
Thyroid gland
follicle cell receptors
25.
26. Other FactOrs regulating thyrOid hOrmOne
levels
• Diet: a high carbohydrate diet increases T3 levels, resulting
in increased metabolic rate (diet-induced thermogenesis).
• Low carbohydrate diets decrease T3 levels, resulting in
decreased metabolic rate.
• Cold Stress: increases T3 levels in other animals, but not in
humans.
• Any condition that increases body energy requirements (e.g.,
pregnancy, prolonged cold) stimulates hypothalamus
TRH TSH.
27. 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 or increase Basal Metabolic
Rate(BMR).
28. • 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)
29. 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)
30. 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(BMR increases).
T3 also acts on mitochondria to increase ATP synthesis(size and
number of mitochondria will increase).
The resulting increased metabolic rate increases thermo genesis
(heat production).
32. thyrOid hOrmOne actiOns which increase
Oxygen cOnsumPtiOn
• Increase mitochondrial size, number and key enzymes.
• Increase plasma membrane Na-K ATPase activity.
• Increase futile(ineffective) thermogenic energy cycles.
• Decrease superoxide dismutase activity.
33. 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
34. eFFects OF thyrOid hOrmOnes On the
resPiratOry system
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia and hypoxia
35. eFFects OF thyrOid hOrmOnes On the renal
system
• Increase blood flow
• Increase glomerular filtration rate(GFR)
36. eFFects OF thyrOid hOrmOnes On Oxygen-
carrying caPacity
• Increase RBC mass
• Increase oxygen dissociation from hemoglobin
37. 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
38. 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.
39. 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
40. 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
41.
42. 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.
Causes:
(a) Insufficient iodine.
(b) Lack of thyroid gland.
(c) Lack of hormone receptors.
(d) Lack of TH binding globulin.
43. how is hypothyroidism rElatEd to 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.
44. midwEst – thE GoitEr bElt
• If goiter is due to decreased I, then thyroid gland enlarges – called
endemic or colloidal goiter.
• Pituitary gland TSH stimulate thyroid gland to produce TH, but
the only result is that the follicles accumulate more and more
unusable colloid.
• Cells eventually die from over activity and the gland atrophies.
