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. _______________________________________