Flashcards in thyroid hormones Deck (40):
where is T3 and T4 synthesized from
iodinated derivatives of tyrosine
what enzyme is responsible ofr "coupling", and what is the coupling process?
thyroid peroxididase: couples DIT with MIT or DIT with DIT to form T3 and T4
where is iodinated tyrosine residue contained?
where was thyroglobulin made and secreted to?
made in follicular cells and secreted through apical membrane into colloid. it's a major component of colloid
what is "organification" of iodine
incorporation of iodine into thyroglobulin
Low dietary iodine intake can cause what? what is the characteristic of this disease?
Goiter: enlarged thyroid gland
elevated TSH drives the growth
Where is iodide derived from
iodine from diet
what is iodide used for during oxidation
to reduce H2O2 into water
and I- gets oxidized into I or I+ to react with tyrosine in thyroglobulin to form MIT or DIT
what enzyme is responsible for organification
what does very high thyroglobulin content mean?
thyroid gland has significant storage capacity: 2-3 months supply
what is required for T3 and T4 release from thyroglobulin
proteolysis of thyroglobulin where it is taken back up into follicular cells via endocytosis and broken down by lysosome
Proteolysis releases T3, T4, MIT, DIT and peptides
How does thyroglobulin get into bloodstream? and what can this be used as?
Thyroglobulin can be TRANSCYTosED into blood stream,
this could be used as tumor marker for increased level indicate graves disease or thyroiditis
what releases thyrotropin releasing hormone (TRH)?
what is the process of TRH for thyroid hormone release
TRH released from hypothalamus goes to anterior pituitary by portal hypophysial system. TRH binds to G protein coupled receptor-->activates phospholipase C-->Ca release triggers exocytosis of vesicles containing TSH
HOw is T4 converted to T3 and where does thi conversion occur
deodination type II, and occurs in liver and kidneys
what causes increases levels of free thryoid hormones? what reduces free thyroid hormone in circulation?
disease states decrease protein synthesis (thyroid hormone binds to serum protein--albumin/transtheyretin--in circulation) and will promote increased levels of free thyroid hormone
Preganancy reduce free thryoid hormone bc it increases plasma protein synthesis.
what hormones inhibit TSH secretion
somatostatin and dopamine
what is T3 and T4 usually bound to? why?
they are hydrophobic so needs to bind to carrier proteins in order to INCREASE half life, bc free T3 and T4 cleared in kidneys
-thyroid binding globin
does T3 or T4 have longer 1/2 life
T4 because it it binds to protein more tightly
what are the differences between T3 and T4
T3 is more biologically active
-it binds to serum portein less tightly
-binds to thyroid hormone receptors MORE tightly
-deiodination converts T4 to T3-->cause activation
what does deiodination mean? what do deiodinases do?
modifying thyroid hormone activity. it helps control thyroid hormone levels
major sites of deoidination?
liver and kidney
what is the role of TSH
Increase Na/I symporter--> increase iodide transport into follicular cells to produce more thyroid hormones .
-increase thyroglobulin synthesis
-thyroid peroxidase action promoting oxidation of iodide and transport onto thyroglobulin
what are the various levels of feedback control
TRH release is inhibited by T2 in circulation and local deiodinase activity in hypothalamus and anterior pituitary gand.
T3 regulates TRH receptor expression on ant pituitary gland thyrotrophs reducing the ability to produce/secrrete TSH.
T3 also regulates amt of mRNA for TSH
which class is the major source of circulating T3; production of T4-->T3 in peripheral tissues
which class is MOST important in control of thyroid hormone release.
which class is considered to be MAJOR physiological terminator of thyroid action in peripheral tissue
which class Converts T4-->T3
which class does NOT convert T4 to T3
which class inactivates both T4 and T3
if theres high T3, what does it induce?
expression of Type III deodinase to promote destruction of T3
what role does glucuronidation play in thyroid hormone metabolism? where does it occur?
Occurs in liver;
Glucuronic acid is added to phenolic hydroxyl group of thyroid hormone promoting water solubility of thyroid hormones.
If also facilitates in elimination in bile
What are some processes regulated by Thyroid hormone
its virtually in all tisues
-increase basal metabolic rate
-increase C.O.(increase HR, decrease peripheral vascular resistance)
-regulate carb and lipid metabolism
-bone turnover (increased bone resorption and bone formation)
-hematopoietic effects: increase O2 demand and erythropoietin production -->increase erythrocytes
-increase gut motility
-increase endocrine metabolic synthesis clearance, responsiveness
excessive head production, nervousness, insonmia, increased HR, weight loss, increased appetite
-antibodies bind to TSH receptor: release Thyroid hormone irrespective of TSH levels
-increased sensitivity to cold
-decreased basal metabolic rate
-weight gain w/o increase caloric intake
-antibodies to thyroid peroxidase, thyroglobulin, TSSSH receptor blocking antibodies-->decrease T3/T4 hormone production
decreased hormone production/secretion
how do thyroid hormones enter target cells
cross plasma membrane via entering cell and binding to soluble receptor molecules due to high affinity/low capcity transport protein.
uptake is an active process and require energy of sodium electrochemical gradient
Thryoid hormone binding process
binds to DNA as heterodimer. other components of dimer is often retinoid X receptor (RXR)--> thryoid hormone triggers confirmational change of receptor-->HDAC is release and histone acetylase (HAT) replaces it-->relaxation of chromatin and enhance transcription