2. LEARNING OBJECTIVES
By the end of the lecture you should be able to :
• Differentiate between Genomic and non-
genomic Effects of Thyroid Hormone.
• Describe metabolic and non metabolic effects of
thyroid hormone.
3.
4. 1-THYROID HORMONES
INCREASE TRANSCRIPTION OF
LARGE NUMBERS OF GENES
Therefore, in all cells of the body, protein enzymes,
structural proteins, transport proteins, and other
substances are synthesized.
5. Thyroid Hormones Activate
Nuclear Receptors
• The thyroid hormone receptors are either
attached to the DNA genetic strands or
located in proximity to them.
• The thyroid hormone receptor usually forms a
heterodimer with retinoid X receptor (RXR) at
specific thyroid hormone response elements
on the DNA.
• After binding with thyroid hormone, the
receptors become activated
6. • Transcription process is initiated.
• Different types of messenger RNA are formed,
• RNA is translated on the cytoplasmic
ribosomes to form new intracellular proteins.
7. Nongenomic Cellular Effects
• Nongenomic actions of thyroid hormone are
independent of their effects on gene
transcription.
• These effects occur within minutes
• Include the regulation of ion channels and
oxidative phosphorylation involving the
activation of intracellular secondary
messengers such as:
cyclic adenosine monophosphate (cAMP) or
protein kinase signaling cascades.
8. 2-THYROID HORMONES INCREASE
CELLULAR METABOLIC ACTIVITY
Thyroid hormone increases:
• The basal metabolic rate
• The rate of utilization of foods for energy.
• The rates of protein synthesis and protein catabolism.
• The growth rate of young people.
• The mental processes and the activities of most of the
other endocrine glands.
• The number and activity of mitochondria
• Active transport of ions through cell membranes
9. Thyroid Hormone Regulates
Mitochondrial Activity
• T3 is considered the major regulator of mitochondrial
activity
– A potent T3-dependent transcription factor of the
mitochondrial genome induces early stimulation of
transcription and increases transcription factor (TFA)
expression
– T3 stimulates oxygen consumption by the mitochondria
10. Thyroid Hormones Stimulate Metabolic
Activities in Most Tissues
• Thyroid hormones (specifically T3) regulate rate of
overall body metabolism
– T3 increases basal metabolic rate
• Calorigenic effects
– T3 increases oxygen consumption by most peripheral
tissues
– Increases body heat production
11. 3-EFFECT OF THYROID HORMONE
ON GROWTH
• Thyroid hormone initiates or sustains differentiation and
growth
– Stimulates formation of proteins, which exert trophic
effects on tissues
– Is essential for normal brain development
• Thyroid hormone has both general and specific effects on
growth.
• Essential for childhood growth and development of the
brain during fetal life and for the first few years of
postnatal life
12. Thyroid Hormones and the Central Nervous
System (CNS)
• Thyroid hormones are essential for neural
development and maturation and function of
the CNS
• Decreased thyroid hormone concentrations
may lead to alterations in cognitive function
– Patients with hypothyroidism may develop
impairment of attention, slowed motor function,
and poor memory
– Thyroid-replacement therapy may improve cognitive
function when hypothyroidism is present
13. Thyroid Hormone is Critical for Normal Bone
Growth and Development
• T3 is an important regulator of skeletal maturation
at the growth plate
– T3 regulates the expression of factors and other
contributors to linear growth directly in the growth
plate
– T3 also may participate in osteoblast differentiation and
proliferation, and chondrocyte maturation leading to
bone ossification
14. 4-EFFECTS OF THYROID HORMONE
ON SPECIFIC BODY FUNCTIONS
Metabolic Effects of T3:
• Stimulates lipolysis and release of free fatty acids and
glycerol
• Induces expression of lipogenic enzymes
• Effects cholesterol metabolism
• Stimulates metabolism of cholesterol to bile acids
• Facilitates rapid removal of LDL from plasma
• Generally stimulates all aspects of carbohydrate
metabolism and the pathway for protein degradation
15. Stimulation of Carbohydrate Metabolism
• Rapid glucose uptake by cells,
• Enhanced glycolysis,
• enhanced gluconeogenesis,
• increased rate of absorption from the GIT,
• increased insulin secretion
16. Stimulation of Fat Metabolism.
• lipids are mobilized rapidly from the fat tissue,
decreasing the fat stores of the body and
increasing the free fatty acid concentration in the
plasma and accelerating the oxidation of free
fatty acids by the cells.
Effect on Plasma and Liver Fats.
• decreases the concentrations of cholesterol
,phospholipids, and triglycerides in the plasma,
even though it increases the free fatty acids.
• Increased Requirement for Vitamins
• Increased Basal Metabolic Rate.
17. Decreased Body Weight. However, this effect does
not always occur because thyroid hormone also
increases the appetite
Increased Respiration.
Increased Gastrointestinal Motility.
Excitatory Effects on the Central Nervous System.
Increases the rapidity of cerebration. A person with
hyperthyroidism can have:
• extremely nervousnous
• many psychoneurotic tendencies: anxiety
complexes, extreme worry, and paranoia
18. Effect on the Function of the Muscles.
•A slight increase in thyroid hormone →makes the
muscles react with vigor,
•An excessive increase in thyroid hormone → the
muscles become weakened because of excess
protein catabolism.
• Lack of thyroid hormone → the muscles become
sluggish, and they relax slowly after a contraction.
Muscle Tremor:
hyperthyroidism → a fine muscle tremor caused by
increased reactivity of the neuronal synapses in the
areas of the spinal cord that control muscle tone.
19. Thyroid Hormone Influences
Cardiovascular Hemodynamics
• Increased Blood Flow and Cardiac Output.
Increased metabolism in the tissues causes rapid
utilization of oxygen and the release of greater
quantities of metabolic end products from the
tissues→ vasodilation in body tissues → increasing
blood flow → increasing cardiac output in the skin
especially increases because of the increased need
for heat elimination from the body.
Increased Heart Rate. Thyroid hormone seems to
have a direct effect on the excitability of the heart
20. Increased Heart Strength. However, when
thyroid hormone is increased markedly, heart
muscle strength becomes depressed because of
long-term excessive protein catabolism.
Normal Arterial Pressure.
21. Effect on Sleep.
Persons with hyperthyroidism have a feeling of
constant tiredness because of the exhausting
effect of thyroid hormone on the musculature and
on the central nervous system, but it is difficult to
sleep because of the excitable effects of thyroid
hormone on the synapses,.
Persons with hypothyroidism show Extreme
somnolence (excessive sleep), with sleep lasting 12
to 14 hours a day.
22. Effect on Other Endocrine Glands.
• Increased thyroid hormone increases the rates of
secretion of other endocrine glands, but it also
increases the need of the tissues for the hormones.
•For example,↑ thyroxine secretion→ ↑ rate of
glucose metabolism in the body → ↑ insulin
secretion by the pancreas.
• thyroid hormone ↑ many metabolic activities
related to bone formation → ↑ the need for
parathyroid hormone.
23. Thyroid Hormone Influences the
Reproductive System
Hypothyroidism:
Menstrual disorders Menorrhagia and
Polymenorrhea, and occasionally even Amenorrhea
(absence of menstrual bleeding), greatly decreased
libido ,infertility, risk of miscarriage.
Hyperthyroidism:
Oligomenorrhea (greatly reduced bleeding)
occasionally Amenorrhea.