Download FUNCTIONS OF THYROID HORMONE

FUNCTIONS OF THYROID HORMONE
LEARNING OBJECTIVES
• At the end of the lecture, the student should be able to :
– Describe the functional anatomy of the Thyroid Gland.
– Know the steps of production of thyroid hormones.
– Tell the Effects of Thyroid hormones on BMR.
– Describe the effect on metabolism of protein,
carbohydrate and fat.
THYROID GLAND:
I. Functional Anatomy
• largest endocrine glands in
the body,
• weighting about 20 – 25g.
 Composed of large
numbers of closed follicles filled with colloid and lined
with a layer of cuboidal epithelioid cells.
 Thyroid hormones are synthesized and secreted by the
epithelioid cells but stored in colloid.
II. PRODUCTION OF THYROID HORMONES
 Iodide (I-) actively transported into the follicle and secreted
into the colloid.
Oxidized to iodine (Io).
H2O2
Hydrogen
Peroxide.
Iodine attached
tyrosine within
to
thyroglobulin chain.
– Attachment of 1 iodine produces monoiodotyrosine
(MIT).
– Attachment of 2 iodines produces diiodotyrosine
(DIT).
THYROID HORMONE SYNTHESIS:
DIT + DIT = THYROXINE (T )
4
3, 5, 3’, 5’-TETRAIODOTHYRONINE
MIT + DIT = TRIIODOTHYRONINE (T )
3, 5, 3’-TRIIODOTHYRONINE
T4 and T3 are still attached to
thyroglobulin within the colloid .
• Upon stimulation by TSH,
3
cells of follicle take up a small volume of colloid by pinocytosis,
• hydrolyze the T3 and T4 from thyroglobulin, and
• secrete free hormones into the blood.
II.
BIOLOGICAL ACTIONS OF THYROID
HORMONES:
 T3 and T4 (Almost all is deiodinated by one iodide ion,
forming T3) bind with nuclear receptor,
 Activate and initiate genetic transcription. ---- mRNA
 Protein synthesis in cytoplasmic ribosomes ---general increase in functional activity throughout the
body.
ON METABOLISM:
 Calorigenic action of thyroid hormones
• increase O2 consumption of most
tissues in the body,
• increasing heat production and BMR.
Mechanism of calorigenic effect of
thyroid hormones may be:
A: Enhances Na+-K+ ATPase activity.
B: Causes cell membrane of most cells to become leaky to
Na+ ions, which farther activates sodium pump and
increases heat production.
 Effect on metabolism of protein, carbohydrate and fat:
 On Protein Metabolism.
Normally, T4 and T3 stimulates proteins synthesis and
enzymes, increasing anabolism of
protein and causing positive
balance of nitrogen.
In hyperthyroidism, catabolism of
protein increases, especially
muscular protein, which leads
weigh-loss and muscle weakness.
HYPOTHYROIDISM:
2) On carbohydrate metabolism:
A: Increase absorption of glucose from the gastrointestinal
tract
E: Enhance glycogenolysis, and even enhanced
diabetogenic effect of glucagon, cortisol and growth
hormone.
C: Enhancement of glucose utilization of peripheral tissues.
3) Effect of Thyroid Hormones On fat metabolism:
• Accelerate the oxidation of free fatty acids by cells.
• Increase the effect of catecholamine on decomposition of
fat.
• Promote synthesis of cholesterol.
• Also increase decomposition of cholesterol by liver cells.
• Net effect of T3 and T4 is to decrease plasma cholesterol
concentration because the rate of synthesis is less than that
of decomposition.
2. EFFECT OF THYROID HORMONES ON
GROWTH AND DEVELOPMENT:
• Essential for normal growth and development especially
skeletal growth and development.
• Stimulate formation of dendrites, axons, myelin and
neuroglia.
• A child without a thyroid gland will suffer from critinism,
which is characterized by growth and mental retardation.
• Without specific thyroid therapy within three months after
birth, the child with cretinism will remain mentally
deficient throughout life.
3. EFFECTS OF THYROID HORMONE ON
NERVOUS SYSTEM:
Thyroid hormones increase
excitability of central nervous
system.
In hyperthyroidism, the patient is
likely to have extreme
nervousness, many
psychoneurotic tendencies
including anxiety complexes,
extreme worry and paranoia, and
muscle tremor.
Thyroid hormones can also
stimulate the sympathetic
nervous system.
The hypothyroid individual is to
have fatigue, extreme
somnolence, poor memory and
slow mentation.
4. OTHER EFFECTS OF THYROID HORMONE:
(1)
EFFECT ON CARDIOVASCULAR SYSTEM
Significant effect on cardiac output because of increase in
heart rate and stroke volume, (may through enhance
calcium release from sarcoplasmic reticulum).
(2)
EFFECT ON GASTROINTESTINAL TRACT:
 Increase the appetite and food intake by metabolic rate
increased.
 Increase both the rate of secretion of the digestive juices
and the motility of the gastrointestinal tract.
 Lack of thyroid hormone can cause constipation.
IV REGULATION OF THYROID HORMONE
SECRETION:
1. Hypothalamic Pituitary Thyroid Axis
(1)
Effect of TSH
 Increase secretion of T4 and T3 by proteolysis of
thyroglobulin
 Increase synthesis of thyroid hormones.
 through enhancement
of ioidide trapping,
ioidination of tyrosine
and coupling to form
hormones
 Stimulate thyroid gland
to growth, increasing
size and number of thyroid cells.
(2) TRH secreted by hypothalamus causes the anterior pituitary
to produce and release of TSH.
• Cold and various emotional reactions can increase TRH
secretion through nervous system and then indirectly affect
the secretion of TSH and thyroid hormones.
2. FEEDBACK MECHANISMS OF THYROID
HORMONES:
T3 and T4
inhibitory protein
in anterior pituitary
reduces production and secretion
of TSH,
decrease response of pituitary to
TRH.
Because of the negative
mechanism, the concentration of
free thyroid hormone in the blood
can be maintained within a
normal range.
• In the absence of sufficient dietary iodide the thyroid
cannot produce adequate amounts of T4 and T3.
• The resulting lack of negative feedback inhibition causes
abnormally high level of the TSH secretion, which in turn
stimulate the abnormal growth of the thyroid (a goiter).
• In the absence of sufficient dietary iodide the thyroid
cannot produce adequate amounts of T4 and T3.
• The resulting lack of negative feedback inhibition causes
abnormally high level of the TSH secretion, which in turn
stimulate the abnormal growth of the thyroid (a goiter).
3. AUTOREGULATION OF THYROID HORMONE
SECRETION:
• Without control of TSH, the thyroid gland can adapt itself
to iodide uptake, which is the autoregulation of thyroid
gland.
• In normal individuals, large doses of iodide act directly on
the thyroid gland to produce a mild and transit inhibition of
hormone synthesis.
• When iodine is insufficient, the thyroid gland increases
formation of hormones.
In patients with hyperthyroidism,
• Iodides cause colloid to accumulate and the vascularity of
hyperplastic gland to decrease.
4. Effect of Autonomic Nervous System on Thyroid
Activity:
• The thyroid gland is innervated by both sympathetic nerve
and parasympathetic nerve.
• Electrical stimulation of sympathetic nerve increases
formation of thyroid hormones
• while stimulation of cholinergic fibers (vagus nerve)
inhibits secretion of thyroid hormone.
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