Endocrine 5: Thyroid Hormone

Question 1

enumerate Hormones secreted by thyroid gland

Answer 1

Thyroid hormones:
* Thyroxin (T4)
* Tri-iodothyronine (T3)

Thyrocalcitonin

Question 2

Describe formation of thyroid hormones

Answer 2

1.Thyroglobulin (colloid) synthesis:
* gycoprotein rich in tyrosine aa
* It’s then secreted into Cavity of thyroid follicle along with peroxidase enzyme

2.Iodide trapping:
* Na+ K+ATPase pumps Na+ out of cell, decreasing its concentration inside the cell
* Na+ is then Cotransported with I- (iodide) inside the cell
* Iodide is co-transported against electrochemical gradient by 8:1

3.Oxidation & Iodination:
* Peroxidase oxidised Iodide into iodine
* Peroxidase binds iodine to thryoglobulin
* this forms MIT & DIT (mon-iodo & di-iodo tyrosines)

4. Coupling:
   * 2 DIT form T4
   * 1 DIT & 1 MIT form T3
   * 1 MIT & 1 DIT form rT3
5. Release:
   * transported into cell by pinocytosis
   * pinocytic vesicle merges with lysosome, where proteinase liberates T4, T3, & remaining DIT & MIT of thyroglobulin
   * T4 & T3 diffuse to nearby capillaries
   * DIT & DMT have their Iodine removed by Iodotyrosine deiodinase enzyme
   * the Iodine is then recycles to make more T3 & T4

6.Storage of excess hormones in center of follicle

Question 3

Other sites of iodide trapping in the body

Answer 3

• Mammary gland
• salivary gland
• gastric mucosa
• placenta

Question 4

ratio of T4:T3:rT3

Answer 4

40:2:1

Question 5

Daily Iodine requirements

Answer 5

500 micrograms:
* 4/5 are rapidly excreted by th kidney
* 1/5 (100 micrograms) undergo iodine trapping

Question 6

Describe how the body can cover any deficiency in daily iodine intake

Answer 6

Storage of Thyroid hormones central follicular cavity

covers up to 2-3 months of deficient intake

Question 7

Thyroid gland secretes ____ micrograms of thyroid hormones per day

Answer 7

70 micrograms per day

93% T4, 7% T3

Question 8

Percentage of T4 that is bound

Answer 8

99.98%

Question 9

Percentage of T3 that is bound

Answer 9

99.8 %

Question 10

Thyroid hormones are carried in the blood via:

Answer 10

• Albumin
• Thyroxine binding prealbumin (TBPA)
• Thyroxine binding globulin

Question 11

which carrier has the highest affinity to thyroid horomones

Answer 11

globulin:
* 2/3 of T4
* 1/2 of T3

Question 12

least active/ inactive thyroid hormone

Answer 12

rT3

Question 13

Most active thyroid hormone, and why

Answer 13

T3:
* More free (less bound to plasma proteins)
* 10-15 more affine to thyroid receptors than T4

Question 14

T3 binds to what type of thyroid receptors

Answer 14

T3= 3 receptors
all beta + alpha 1
* Beta 1
* Beta 2
* Alpha 1

Question 15

sites of thyroid receptors

Answer 15

• Extranuclear for non-genomic actions (cell membrane, cytoskeleton, cytoplasm mitochondria)
• Nuclear (bound to DNA) for genomic actions

Question 16

effect of thyroid hormone on genral cellular metabolism

Answer 16

Calorigenesis & Increases O2 Consumption:
* Increase in number & Size of mitochondria - In excess, may lead to mitochondrial swelling & uncoupling of oxidative phosphorylation with little increase in ATP and greater loss of heat
* Increases the activity of Sodium potassium pump

Question 17

effect of thyroid hormone on Carbohydrate metabolism

Answer 17

• increase insulin secretion
• Increase glucose uptake by the cell
• increase glucose absorption by GIT
• Increase glycolysis
• Increase gluconeogenesis

Question 18

effect of thyroid hormone on Lipid metabolism

Answer 18

overall decrease in blood lipids:
* Lipolysis & mobilization of lipids from fat tissue
* Increase FFA oxidation
* Decrease plasma cholesterol by:
1.increase cholesterol secretion in bile
2.increase LDL receptors of liver –> rapid removal of LDLs from plasma
3.Increase cholesterol oxidation by the cells

Question 19

effect of thyroid hormone on Protein metabolism

Answer 19

(anabolic) increases protein synthesis

Question 20

effect of thyroid hormone on Vitamin metabolism

Answer 20

general increase in enzyme activity —> increase in body reqirements for coenzymes (vitamins)

Question 21

effect of thyroid hormone on BMR, BEE & body weight

Answer 21

normal levels of TH are responsible for normal BMR & BEE (40 calories/hr/m2) & normal body weight = energy balance

Question 22

effect of thyroid hormone on growth

Answer 22

• Mental growth and development
• Neuronal, axonal & nerve ending formations
• Skeletal growth
• Sexual growth (along with hormones)

Question 23

effect of thyroid hormone on body systems

Answer 23

• primary effect: direct hormonal action
• secondary effect: increase metabolism of various systems –> caloregic action (increase O2 consumption)

Question 24

where in the body does o2 consumption decrease by thyroid hormone

Answer 24

Anterior pituitary gland (negative feedback)

Question 25

where in the body does o2 consumption doesn't increase by thyroid hormone

Answer 25

* Testis & uterus * ADULT brain * Spleen * Lymph nodes

Question 26

Describe the hypothalamic -pituitary regulation of Thyroid hormone

Answer 26

1. Hypothalamus secretes TRH (thyrotropin releasing hormone) through hypothalamo-hypophyseal portal circulation 2. TRH binds to thyrotrope receptors in Anterior pituitary --> G protein --> phosphlipase --> increase intracellular Ca2+ --> release of Thyrotropin/ Thyroid stimulating hormone into systemic circulation 3. TSH binds to receptors on basal mmebrane of thyroid gland cells ---> G protein --> Adenyl cyclase --> cAMP --> protein kinase --> phosphorylations Witihin 30 mins of phosphorylation: increased thyroglobulin proteolysis Within hours, days weeks: Activation of iodide pump making 8:1 iodide (intracellular to extracellular) + increase tyrosine iodinasation + increase in number & size of thyroid gland cells

Question 27

describe feedback regulation of thyroid hormones

Answer 27

done by T3: * both T3 & T4 directly decrease TSH/thyrotropin production in pituitary gland * T4 is converted first to T3 to exert feedback effect