Thyroid hormone effect on human body and its function

Action of thyroid hormone

1. ACTIONS OF THYROID
HORMONE
Presented by:-Pankaj Singh
Roll. No. 46
1st yr BHMS

2. ●PHYSIOLOGICAL EFFECTS OF THYROID HORMONES

●Mechanism of Action

●Physiological Actions
Effect On:
Basal metabolism
Thermogenic effect
Nervous system
CVS
Growth and development
Intermediatey Metabolism
Sympathetic neurones system
Respiratory system
GI. Tract
Skeleton muscle, reproduction system, kidney
LEARNING OBJECTIVES ##:

3. MACHANISM OF ACTION
●The mechanism of action of thyroid hormones is similar to that of steroid
hormones.
●They act by binding with the intracellular receptors.

●With few exceptions like adult brain and gonads, receptors for thyroid hormones
are present in all tissues and organs.

●Though the developing neurons in infants and children are highly sensitive to
thyroid hormones,

●It is not clear why the adult neurons are not so sensitive.

4. 1. **Cellular Entry**: T3 and T4 enter target cells via carrier-mediated,
energy-dependent transport.

2. **Conversion and Binding**: T4 is mostly converted to T3 inside the cell,
which then binds to thyroid hormone receptors (TR) located on the nucleus.

3. **Gene Activation**: T3 binding to TR-TRE complexes on DNA stimulates
transcription of mRNA.

4. **Protein Synthesis**: Increased mRNA leads to enhanced intracellular
protein synthesis, promoting cellular growth, maturation, enzyme synthesis,
mitochondria formation, and respiratory enzyme production.

5. 5. **Metabolic Effects**: Enhanced Na+-K+ ATPase activity increases cellular
oxygen consumption, while increased mitochondrial activity boosts overall
cellular metabolism.

7. THYROID hormone receptors (TR):

1. **Gene Location**: TRα gene on chromosome 17, TRβ gene on
chromosome 3.
2. **mRNA Synthesis**: Each gene synthesizes two different mRNAs,
forming TRα1, TRα2, TRβ1, and TRβ2.
3. **Tissue Distribution**: TRα1 and TRβ1 widely distributed; TRα2 does
not bind T3 and function not well understood; TRβ2 found only in the brain.
4. **Binding Specificity**: T3 binds more rapidly and avidly to TR compared
to T4; T3 is more potent.
5. **Direct Action in Myocytes**: In heart myocytes, T3 directly enters to
bind nuclear receptors, influencing gene expression directly.

8. THYROID HORMONE
EFFECTS

9. Effects on Growth and Development

### Growth and Musculoskeletal Maturation
1. **GH Expression**: Promote growth hormone gene expression in the anterior
pituitary.
2. **GH Facilitation**: Enhance the effect of GH on tissues.
3. **Bone Growth**: Stimulate linear bone growth, endochondral ossification, and
maturation of epiphyseal bone centers.
4. **Chondrocyte Activity**: Enhance chondrocyte activity in cartilage.
5. **Bone Remodeling**: Increase osteoid activity and bone remodeling.
6. **Teeth Development**: Cause eruption and development of teeth.

10. 7 Epidermal Growth**: Promote epidermal growth, nail, and hair growth.
8. **Protein Synthesis**: Stimulate synthesis of structural and enzymatic proteins.

### Hypothyroid Effects in Children
9. **Bone Growth**: Slowed bone growth and delayed epiphyseal closure.

### Tissue Effects
10. **Mucopolysaccharides**: Alter characteristics of mucopolysaccharides in
subcutaneous tissue, decreasing synthesis and promoting degradation of
glycosaminoglycans.

12. #. Cardiovascular**:
- Increased cardiac output.
- Increased tissue blood flow.
- Increased heart rate.
- Increased heart strength.
- Increased respiration.

13. 2. Metabolism**:
- Increased mitochondrial activity.
- Increased Na⁺-K⁺-ATPase activity.
- Increased O₂ consumption.
- Increased glucose absorption.
- Increased gluconeogenesis.
- Increased glycogenolysis.
- Increased lipolysis.
- Increased protein synthesis.
- Increased basal metabolic rate (BMR).

14. General Effects on Basal Metabolism

### Oxygen Consumption and Basal Metabolism
1. Increase basal rate of oxygen consumption.
2. Elevate basal metabolism and heat production (calorigenic effect).

### Cellular Metabolism Activation
3. Activate Na+-K+ ATPase activity.
4. Oxygen consumption parallels Na+-K+ ATPase activity.
5. Inhibition of Na+-K+ pump decreases oxygen consumption.
6. T3 stimulates Na+-K+ pump gene transcription.

### Target Tissues
7. High response: skeletal muscle, liver, heart, kidney, connective tissues.
8. Low response: anterior pituitary, adult brain, gonads, uterus, lymph nodes, spleen.

.

15. ### Basal Metabolic Rate (BMR)
9. Resting oxygen consumption: 250 mL/min.
10. Hyperthyroidism: oxygen consumption ~400 mL/min, BMR +80%.
11. Hypothyroidism: BMR -40%.
12. Increased BMR raises body temperature.

### Mitochondrial Mechanism
13. Increase mitochondrial cytochromes synthesis.
14. Promote cytochrome oxidase activity.
15. Regulate respiratory units and oxidative phosphorylation capacity.
16. Stimulate UCP-1 synthesis.
17. Increase UCP-2 and UCP-3 expression

16. #@#Effects on Nervous System

### Developmental Effects
1. **Brain Development**: Critical for brain development during the last six
months of fetal life and first six months postnatally.
2. **Cell Differentiation**: Facilitate differentiation and maturation of brain
cells.

### Neural Functions
3. **Growth**: Promote growth of cerebral and cerebellar cortices, and basal
ganglia.
4. **Axon Proliferation**: Encourage axon proliferation and dendrite
branching.
5. **Synaptic Development**: Essential for the development of synaptic
connections.

17. 6 Neurotransmitter Systems**: Aid in the development of
neurotransmitter systems by inducing enzyme formation.
7. **Receptor Increase**: Increase the number of
neurotransmitter receptors in the brain.
8. **Myelination**: Stimulate myelin formation by enhancing
galactosyl sialyl transferase activity.
9 protein Synthesis**: Support synthesis of proteins and
enzymes like succinic dehydrogenase needed for neuronal
energy.

18. 10. **Cell Migration**: Facilitate cell migration during brain development.

### Cognitive and Reflex Functions
11. **Alertness**: Enhance general alertness and responsiveness.
12. **Reflexes**: Improve speed and amplitude of stretch reflexes.
13. **Cognitive Abilities**: Influence memory, learning, and intellectual
capacities.

### Deficiency Effects
14. **Infant Deficiency**: Leads to irreversible retardation in CNS development
if untreated.
15. **Adult Brain Function**: Normal cerebral blood flow, glucose, and oxygen
utilization in hypothyroidism and hyperthyroidism.

19. ## Additional Notes
16. **Hormone Conversion**: T4 is converted to T3 by astrocytes in the adult
brain.
17. **Post-Thyroidectomy**: Increased D2 deiodinase activity
post-thyroidectomy, reversed by T3 injection.

20. ### Heart RateCardiovascular Effects

1. **Increase HR**: More β receptors and increased sensitivity on SA/AV nodes.
2. **Tachycardia**: Common in hyperthyroidism.

### Myocardial Contractility
3. **Myosin Heavy Chain (MHC)**: Increase α-MHC (high ATPase activity), decrease
β-MHC (low ATPase activity).
4. **β Receptors and Proteins**: Increase β receptors, G proteins, Na+-K+ ATPase in
myocardial cells.

21. 5 Calcium-ATPase**: Increase activity in sarcoplasmic reticulum for calcium
sequestration.

### Blood Pressure
6. **Systolic Pressure**: Increased due to higher heart rate and stroke volume.
7. **Diastolic Pressure**: Decreased due to thermogenic cutaneous vasodilation and
lower peripheral resistance.

### Additional Notes
8. **Inhibitions**: Inhibit phospholamban, adenylyl cyclase, T3 nuclear receptor,
Na+-Ca+ exchanger in myocytes.

22. ### Sympathetic Nervous System
1. **Metabolic Synergy**: Synergize catecholamine effects (lipolysis,
glycogenolysis, gluconeogenesis).
2. **β Receptors**: Increase expression and sensitivity in heart, skeletal muscle,
and adipose tissue.
3. **Thermogenin Production**: T3 stimulates thermogenin in brown adipose
tissue, aiding thermogenic action.

### Clinical Notes
4. **Hypersympathetic State**: Hyperthyroidism mimics sympathetic stimulation
effects (e.g., increased metabolism, body temperature, nervousness).
5. **β Blockers**: Alleviate hyperthyroidism symptoms and mildly decrease
plasma T3.

23. ### Respiratory System
6. **Oxygen Utilization**: Increase tissue oxygen utilization.
7. **Respiratory Stimulation**: Stimulate respiration rate, minute ventilation,
and ventilatory responses to hypercapnia and hypoxia.
8. **Arterial PO2**: Increase arterial PO2, enhancing oxygen supply to
tissues.
9. **Erythropoiesis**: Stimulate erythropoiesis by increasing erythropoietin
synthesis.

### Gastrointestinal Tract
10. **GI Motility**: Enhance GI tract motility (hyperdefecation in
hyperthyroidism, constipation in hypothyroidism).
11. **Appetite**: Increase appetite and food intake.
12. **Glucose Reabsorption**: Increase glucose reabsorption from the GI
tract.

24. ### Skeletal Muscle
- **MHC Expression**: Increase MHC gene expression in skeletal muscle.
- **Hypothyroidism**: Associated with muscle cramps and weakness.
- **Hyperthyroidism**: Can lead to muscle weakness due to increased
protein catabolism; chronic cases may result in thyrotoxic myopathy.

### Reproductive System
- **Women**: Promote follicular maturation and ovulation; abnormalities can
cause menstrual irregularities (menorrhagia in hypothyroidism,
oligomenorrhea in hyperthyroidism).
- **Men**: Support spermatogenesis; T3 helps in the differentiation of
prepubertal Sertoli cells.

25. ### Kidney
- **Effects**: Increase kidney size and growth of renal tubular epithelial cells.
- **Renal Function**: Enhance renal blood flow, glomerular filtration rate (GFR), and
tubular reabsorption of electrolytes, glucose, and water.
- **Water Reabsorption**: Increases blood volume through enhanced water
reabsorption.