This document discusses the anatomy, production, transport, regulation, and actions of thyroid hormones T3 and T4, including their biological activity and the importance of iodine intake. It outlines the mechanisms of thyroid hormone regulation by iodine levels and the hypothalamus/pituitary gland, as well as the consequences of thyroid hormone excess (hyperthyroidism) and deficiency (hypothyroidism) on various bodily functions. Additionally, it highlights the roles of thyroid hormones in growth, metabolism, cardiovascular health, and neurological development.

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

2. Histology of theThyroid 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. TheThyroid 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.

4. Thyroid Hormones:
 There are two biologically active thyroid hormones:
- Tetraiodothyronine(T4; usually called thyroxine)
- Triiodothyronine (T3)
 Derived from modification of tyrosine(amino acid).

5. Differencesbetween 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.

6. Major sourcesof 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

7. TheNext 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.

8. 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.

9. 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

10. Regulation of Thyroid HormoneLevels:
• 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.

11. Auto regulation of Thyroid HormoneProduction
• 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.

12. Neuro endocrineRegulation of Thyroid Hormones: Roleof
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.

13. Other FactorsRegulating Thyroid HormoneLevels
• Diet: a high carbohydrate diet increases T3 levels, resulting
in increased metabolic rate (diet-induced thermo genesis).
• 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.

14. Actionsof 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).

15. • 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)

16. Effectsof Thyroid Hormoneon 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)

17. OneMajor Target Geneof T3: TheNa+
/K+
ATPasePump:
 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).

18. Thyroid HormoneActionswhich IncreaseOxygen
Consumption
• Increase mitochondrial size, number and key enzymes.
• Increase plasma membrane Na-K ATPase activity.
• Increase futile(ineffective) thermogenic energy cycles.
• Decrease super oxide dismutase activity.

19. Effectsof Thyroid Hormoneson theCardiovascular
System
• Increase heart rate
• Increase force of cardiac contractions
• Increase stroke volume
• Increase Cardiac output
• Up-regulate catecholamine receptors

20. Effectsof Thyroid Hormoneson theRespiratory System
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia and hypoxia

21. EffectsThyroid Hormonesin 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.

22. Effectsof Thyroid Hormoneson theNervousSystem
• 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

23. Effectsof Thyroid Hormoneson theReproductiveSystem
• Required for normal follicular development and ovulation in the
female
• Required for the normal maintenance of pregnancy
• Required for normal spermatogenesis in the male

24. How isHypothyroidism 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.

25. Midwest – theGoiter 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.

26. Thyroid HormoneExcess: 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.
• Causes:
(a) Excessive TSH release.
(b) Autoimmune disorders.

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