thyroid Flashcards
What is the function of the Thyroid?
Hypothalamic regulation of hormones
What does TRH stand for?
Thyrotropin Releasing Hormone
tri-peptide
What does TSH stand for?
Thyroid Stimulating Hormone
What is TSH and what is it composed of?
pituitary dimeric glycoprotein (~30,000 MW) composed of an alpha and beta subunit.
The alpha subunit of TSH, FSH and hCg is identical what makes them different?
Beta subunits differ and confer biological specificity
What is the role of TSH?
TSH binds to a G protein-coupled receptor on thyroid follicle epithelial cells which activates both:
Adenylate cyclase => cAMP/PKA-dependent pathway
Phospholipase C => PI turnover => DAG and IP3
Describe what Thyroid follicles look like
Hollow spheres of epithelial cells. Lumen filled with a gelatinous colloid consisting of a large protein called THYROGLOBULIN
Describe the synthesis if thyroid hormones? (5)
Thyroglobulin synthesized by thyroid follicular cells and exocytosed into the lumen.
Thyroglobulin contains high content of tyrosine
Iodide is actively taken up from the blood into follicular cells and transported into the lumen
In the lumen, the enzyme thyroid peroxidase converts iodide to free iodine
Iodine atoms incorporated into tyrosine residues (still part of thyroglobulin molecule!)
What is a mono-iodotyrosine (MIT)?
one iodine per tyrosine
What is a di-iodotyrosine (DIT)?
two iodines per tyrosine
Can coupling occur between iodinated tyrosine residues?
DIT + DIT=> T4 or thyroxine
MIT + DIT => T3 or Triiodothyronine
Occurs under oxidising conditions.
(2 MITs do not couple)
Describe the process of releasing thyroid hormone (4)
Follicular cells take up a portion of the colloid in the lumen (endocytosis)
Lysosomal enzymes in the follicular cells break down the iodinated thyroglobulin liberating ‘free’ T3 and T4.
T4 and T3 diffuse through the plasma membrane of the follicular cells into the blood
Inactive MIT and DIT are rapidly deiodinated and the released iodine is recycle back to lumen for further use
What is the function of TGB? (4)
Thyroxine-binding globulin
T3 and T4 circulate bound to TBG (and albumin) as they have poor solubility in water – very little free T3/T4
TBG prevents urinary secretion of T3 & T4
TBG buffers against acute changes in thyroid function
T3/T4 must dissociate from TBG to exert biological effect
T3 vs T4 (3)
Which is secreted more?
Which is more potent?
Which is the active form?
90% is T4 10% is T3
T3 is 4 fold more potent than T4
Most of the secreted T4 is activated by peripheral target tissues by the removal of one iodine to yield T3
Which receptor do T3 and T4 bind to?
hormone-responsive transcription factor