WEEK 2: THYROID HORMONE Flashcards
Describe the secretion of thyroid hormone
- Uptake of iodinated thyroglobulin ( thyroglobulin - hormone complex) by endocytosis by thyrocytes
- Lysosome fuse with the vesicle containing the iodinated thyroglobulin
*Proteolytic enzymes in the endolysosome cleave thyroglobulin into MIT,DIT,T3- and T4 - T3 and T4 are released into fenestrated capillaries via MCT8 transporter
- There is deiodination of MIT and DIT
- The iodine released is then redistributed to intracellular iodide pool
Describe the synthesis process of thyroid hormone
- Synthesis of thyroglobulin by follicular cells and release it into the lumen of follicle
- Iodide uptake by secondary transport into follicular cells ( NA + / I - and NA+ / K +)
3.Oxidation of iodide to iodine by help of thyroperoxidase located in luminal membrane of follicular cells in contact with the coloid - Iodine enters coloid via pendrin transporter
- Attachment of iodine to tyrosine residues giving MIT and DIT ( mono-idothyronine and di-idothyronine)
6 .Coupling of MIT And DIT to form T3-( MIT + DIT) or T4( DIT x2) - Products remain attached to the thyroglobulin by peptide bonds and stored
Describe the regulation of thyroid hormone secretion by the hypothalamus and pituitary gland
- TRH release by hypothalamus
2.Anterior pituitary release TSH
3.TSH stimulates follicular cells to synthesize thyroglobulin
4.Iodide trapping - Iodide oxidation by thyroperoxidase enzyme
6.Iodination of tyrosine residues in the thyroglobulin
7.couple MIT’s and DIT’s
8.Endocytosis it thyroglobulin - hormone complex - Lysosomal enzymes cleave T3 +T4 out of thyroglobulin
10.T3 + T4 released to the blood circulation and bind to plasma proteins ( albumin, Thyroxine binding prealbumin and thyroxine binding globulin)
How does hyperthyroidism occur when a patient is given thiouracil drug?
Thiouracil blocks oxidation of iodide, resulting in thyroid hormones not being produced.There is stimulation of the pituitary gland to release TSH in large quantities causing follicular cells to hypertrophy and absorb colloid very actively from the lumen , reducing it’s size..
Name the enzyme that deiodinates MIT and DIT
Iodinase
How is rT3 formed?
It is formed during conversion of T 4 to T3 when inner ring of T4 is deiodinated
It is an inactive thyroid hormone
*Inner ring deiodination of T4 yields rT3 which is inactive
*Outer ring deiodination yields T3. Therefore, T3 and rT3 are isomers.
*T4 serves as a prohormone for T3
Name the enzymes that changes T4 to T3
Why is T4 changed to T3?
5’ deiodinase
The nuclear thyroid hormone receptors have 10X more affinity for T3 than for T4. Therefore, T3 is more potent than T4.
Outline ways in which thyroid hormones are transported in blood
Bound to:
* Albumin
*Thyroxine binding Globulin (TBG)
*Thyroxine binding prealbumin (TBP)
NOTE: Thyroid hormones are lipophilic, so they are transported bound to plasma proteins
T3 binds more to albumin.
T4 binds more to Thyroxine binding globulin.
What is the % distribution for the following hormones in circulation?
*T3, T4 and rT3
In circulation the distribution of the hormones is:
*90% T4, 9% T3 and 0.9% rT3.
Hypothalamus - Pituitary - Thyroid axis
Negative feedback effect of thyroid gland on TSH and TRH
Differentiate between hypertrophy and hyperplasia
Hypertrophy:increase in cell size
Hyperplasia:increase in number of cells
State another hormone produced by the thyroid gland.
Where is it produced secrete it?
What is the main component of Thyroglobulin?
*Secrete calcitonin.
*C- cells or Parafollicular cells
*Main constituent of colloid in a follicular cell is a glycoprotein called thyroglobulin.
What is the daily iodine intake ?
What is the plasma circulation pool of iodine?
400mg/day
250- 750 mg
State the sources of iodine
*eggs
*Milk
*Yoghurt
*Banana
*Turkey
*Baked potatoes
*Green peas
*Table salt
*Shrimp
*Strawberry
*Cranberry
*Prunes
*Sea weed
*Vegetables
State the effects of thyroid hormone on the heart, CNS, Bone, adipose tissue, muscles, skin, GI tract, lungs, kidney, in children , liver
HEART AND CVS
Increased heart rate
Increased stroke volume
Increased force of contraction
Mechanism is via increased ß-adrenergic receptors and increases in myocardial cell Ca++ concentration.
Systolic pressure is increased.
Diastolic pressure is decreased.
Thyroid hormone has permissive effect on catecholamines.
CNS
Increased dendrites formation
Increased myelination to allow for faster transportation.
Increased number of synapses
Promotes brain development (cerebral and cerebellar cortex)
Increased learning capacity and IQ
BONES AND GROWTH
Regulates balance between osteoclasts and osteoblasts.
Increased interstitial growth.
Stimulation and regulation of endochondral ossification
Plays a role in bone remodeling.
Endochondral ossification
Enhance linear growth of bones after birth.
Maturation of epiphyseal bone center.
Facilitates synthesis and secretion of growth hormone.
ADIPOSE TISSUE
Activates lipolysis.
Decrease excretion of cholesterol by the liver
Reduce plasma cholesterol.
MUSCLES
Stimulates protein catabolism.
SKIN
Sweat production.
REPRODUCTION, ENHANCES:
Female follicular development and ovulation
Testicular process of spermatogenesis
Sustains normal reproductive cycle rhythmicity.
ON SYMPATHETIC STIMULATION
T3 increases number of b-adrenergic receptors in heart muscles.
T3 does not increase level of circulating catecholamines.
GI TRACT
Stimulates secretions on the mucosa of the GIT
Acts on the smooth muscles helping in the Normal motility of the GI tract
LUNGS
Stimulate the respiratory centers and lead to increased oxygenation because of increased perfusion.
KIDNEY
Increased water and Na+ reabsorption by kidney
Tubular maximum transport
Increase glomerular filtration.
Increased renal plasma flow.
In children
Wakefulness
Alertness and responsiveness to various stimuli
Memory
Increased speed and amplitude of reflexes
LIVER
*Glycogenolysis
*Gluconeogenesis
* Increased number of LDL receptors in the liver hence more LDL update in the liver and increases it in the liver where it is metabolized to energy
LACTATION
Increases milk production.
Increases fat content of milk.
DIGESTION
Increase glucose absorption from the gut.
Pancreatic enzyme synthesis & secretion increased.
