ACTIONS OF THYROID HORMONE

1. GENES Thyroid hormone increases the transcription of large number of genes. ↓ Thus, in all cells of the body, there is increased production of: 1.Protein enzymes 2.Structural proteins 3.Transport proteins ↓ Net result: there is generalized increase in functional activity throughout the body!

2. CALORIGENIC ACTION Increases the O 2 consumption of almost all metabolically active tissues + increases activity of the Na-K Pump ↓ Increased metabolic rate (BASAL METABOLIC RATE) (Rate of O 2 consumption & energy expenditure under resting conditions) ↓ Increased Calorigenic effect (increased heat production) ↓ If food intake is not increased, endogenous protein and fat stores are catabolized ↓ Weight loss occurs

3. GROWTH & MATURATION

GROWTH & MATURATION a: Skeletal System At the level of bone formation, thyroid acts synergistically & permissively with GH, IGF-1 & other growth factors. It is required for normal growth hormone synthesis & secretion. Thyroid hormone accelerates bone maturation. (skeletal maturation is different from skeletal growth!) Bone age is, thus, retarded relative to chronological age in children who are deficient in thyroid hormone. In cases that are Hyperthyroid ?

GROWTH & MATURATION b: Central Nervous System Thyroid hormone receptors are present early in the development of the fetal brain, well before the thyroid gland becomes functional. Maturation of the nervous system during the Perinatal period has an absolute dependence on thyroid hormone. ↓ During this period, Thyroid hormone must be present for normal brain development. ↓ It is especially needed for nerve myelination, brain vascularity & normal brain growth! ↓ Thyroid hormone promotes growth & development of the brain during fetal life & for the first few years of postnatal life.

GROWTH & MATURATION b: Central Nervous System If thyroid hormone conc. insufficient both before & after birth, the growth & maturation of the brain are greatly reduced. ↓ Brain remains smaller! (due to decrease in axonal density & dendritic branching & vascularity) Without specific thyroid hormone therapy within days or weeks after birth, the child without a thyroid gland will remain mentally deficient throughout life! ↓ Thus, thyroid hormone deficiency at this stage can be catastrophic & the damage done is irreversible even if large doses of the hormone are given later in childhood!

GROWTH & MATURATION b: Central Nervous System In Adult life: Hyperthyroidism produces: 1.Hyper excitability 2.Irritability 3.Restlessness 4.Exaggerated responses to environmental stimuli 5.Emotional instability 6.Full-blown Psychosis

GROWTH & MATURATION b: Central Nervous System In Adult life: Hypothyroidism produces: 1.Listlessness 2.Lack of energy 3.Slowness of speech 4.Impaired memory 5.Somnolence 6.Dulled mental capacity 7.Psychosis (myxedema madness)

GROWTH & MATURATION POINTS TO REMEMBER: It stimulates growth of the skeletal system. It stimulates normal synthesis & secretion of the GH. It stimulates & promotes normal growth & development of the brain during the perinatal period. Its deficiency during postnatal period can lead to irreversible mental retardation & small sized brain. In the adult, it has excitatory effects on the nervous system.

ACTION OF THYROID HORMONE 3. AUTONOMIC NERVOUS SYSTEM

SYMPATHOMIMETIC EFFECTS Any action similar to one produced by the sympathetic nervous system is called a Sympathomimetic effect. Interactions b/w thyroid hormone & ANS are important throughout life. ↑ secretion of thyroid hormone exaggerates many responses of the sympathetic neurons. It ↑ the number of receptors for epinephrine & NE (beta- adrenergic receptors) in the myocardium & other tissues. Thus, many symptoms of hyperthyroidism resemble sympathetic nervous system.

ACTION OF THYROID HORMONE 4. METABOLISM

a. Carbohydrate metabolism It stimulates all aspects of carbohydrate metabolism 1.↑ uptake of glucose by the cells 2.↑ glycolysis 3.↑ gluconeogenesis 4.↑ rate of absorption of glucose from GIT 5.↑ glycogenolysis 6.↑ secretion of Insulin

b. FATS It stimulates all aspects of Fat metabolism. POINT TO REMEMBER: Thyroid hormone is not the primary determinant for accelerating fat metabolism BUT is acting as GAIN control thus it amplifies the steps without starting them! It stimulates lipid mobilization from fat tissues RESULT?

b. FATS ↑ thyroid hormone ↓ the conc. of cholesterol, PL, and TG in the blood. ↓ thyroid hormone ↑ the conc. of cholesterol, PL, and TG in the blood + causes excessive fat deposition in the liver M.O.A: Increased rate of cholesterol secretion in the bile & consequent loss in the feces. This is done by increasing lipoprotein receptors on the liver cells.

PROTEIN METABOLISM Both synthesis & degradation of proteins are slowed in the absence of thyroid hormones. & accelerated by the thyroid hormones! 1.Increased translation of RNA 2.Increased transcription of DNA to RNA 3.Increased activity of mitochondrias 4.Increased activity of cellular enzymes SO, what will happen in the HYPERTHYROID SUBJECTS?

ACTION OF THYROID HORMONE 5. HEART

BLOOD FLOW & CARDIAC OUTPUT Increased BMR ↓ Increased & more rapid oxygen consumption by the tissues ↓ Greater than normal metabolic end products ↓ Vasodilatation in most tissues ↓ Increased blood flow ↓ Increased cardiac output

HEART RATE Thyroid hormone causes considerably increased heart rate---TACHYCARDIA ↓ A very sensitive symptom thru which the clinician determines whether a patient has excessive or diminished thyroid hormone production

HEART STRENGTH Small increase in thyroid hormone secretion: Increase in heart strength due to increased enzymatic activity (as occurs in mild fevers during exercise) Large increase in thyroid hormone secretion: heart strength becomes depressed b/c of long term protein metabolism Some severely Thyrotoxic patients die of severe cardiac decompensation (due to myocardial failure b/c of increased cardiac output causing increased cardiac load)

ACTION OF THYROID HORMONE 6. RESPIRATION

Increased rate of metabolism ↓ Increased utilization of oxygen + Increased formation of carbon dioxide ↓ Increased rate & depth of Respiration

ACTION OF THYROID HORMONE 7. GASTROINTESTINAL TRACT

Increased appetite Increased food intake Increased GI motility Increased GI secretions SO, Hypothyroidism causes:__________ & Hyperthyroidism causes: __________

ACTION OF THYROID HORMONE 8. MUSCLE

MUSCLE VIGOR Slight increase in thyroid hormone secretion: muscles react with vigor Large increase in thyroid hormone secretion: muscles become weakened b/c of excess protein catabolism. WITH HYPOTHYROIDISM MUSCLES BECOME SLUGGISH & THEY RELAX SLOWLY AFTER A CONTRACTION!

MUSCLE TREMOR Usually seen with hyperthyroidism Fine muscle tremor / sec Observation: place a sheet of paper on the extended fingers & noting the degree of vibration of the paper! Cause: increased reactivity of neuronal synapses

ACTIONS OF THYROID HORMONE 9. SLEEP

SLEEP Increased thyroid hormone secretion ↓ Exhaustive effect on the musculature & CNS ↓ Constant tiredness BUT, b/c of the excitable effects on synapses, IT IS DIFFICULT TO SLEEP

SLEEP In Hypothyroid individuals, there is SOMNOLENCE (Sleep sometimes lasts from 12 to 14 hours)

ACTIONS OF THYROID HORMONE 10. OTHER ENDOCRINE GLANDS

INSULIN Increased rate of Glucose absorption from the GIT and increased rate of gluconeogenesis. ↓ Increased Blood glucose levels ↓ Increase in Insulin Secretion

PARATHYROID HORMONE Increase in bone maturation and stimulation of bone metabolic activities ↓ Increase in Parathyroid Hormone Secretion

GLUCOCORTICOIDS Thyroid hormone increases the rate at which the glucocorticoids are inactivated by the liver ↓ Feedback increase in adrenocorticotropic hormone (ACTH) production by the anterior pituitary ↓ Increased rate of secretion of glucocorticoids by the adrenal glands

11. Effect on Body weight TH is essential for maintaining body weight. Increase in TH → Decreases the Body weight and fat stores. Decrease in TH → Increases the Body weight and fat stores.

12. Action on Blood TH is one of the important GENERAL factors required for Erythropoiesis. ↓ Accelerates Erythropoietic activity leading to an increase in the blood volume. ↓ Polycythemia is common in Hyperthyroidism.

ACTION OF THYROID HORMONE 13. SEXUAL FUNCTIONS

For normal sexual development and function, thyroid hormone production must be normal. ↓ This effect is exerted by: 1.A direct metabolic effect on the gonads 2.Excitatory & inhibitory feedback effects operating through the anterior pituitary.

MALES Lack of thyroid hormone causes complete loss of libido (sexual drive) Excess of thyroid hormone causes impotence

FEMALES Hypothyroidism leads to: - Menorrhagia (excessive bleeding) - Polymenorrhea (frequent menstrual bleeding) - Irregular menstruation - Amenorrhea Hyperthyroidism leads to: - Oligomenorrhea - Amenorrhea