Regulation of Thyroid Hormone Synthesis Flashcards
Primary constituent of the colloid
Thyroglobulin
Components of thyroid hormone
Tyrosine and iodide
hormone T4, also known as thyroxine
3, 5, 3’, 5’ tetraiodothyronine
hormone T3
3, 5, 3’ triiodothyronine
Briefly describe Th synthesis
TH synthesis involves iodination of tyrosine residues, followed by the coupling of iodotyrosines to form the iodothyronines
The mechanism for iodide transport into the gland
“iodide trap” mechanism
- a basal membrane pump in follicular cell accumulates iodide in the thyroid typically 30-40 times that in the serum
- Against chemical/electrical gradient
Describe movement of iodide after transport in follicular cell
- Diffuses from basolateral to apical side (closer to colloid)
- Moving w/ chemical/electrical gradient
- Oxidation of I- to I2 by thyroperoxidase
- Organification of iodide on the cell-colloid interface,
Thryoglobulin strutucure
Thyroglobulin (TG) is a glycoprotein of 660 kD composed of two identical polypeptides
Which compound catalyzes the first step of TH synthesis
thyroperoxidase catalyzes the iodination of tyrosyl moieties on TG. In this way mono- (MIT) and diiodotyrosine (DIT) are formed on TG.
Inhibitors of TH synthesis and effects
thiourea drugs (e.g., propylthiouracil-PTU, and methimazole) and since they lead to enlarged thyroid glands (goiters), they are also termed goitrogen
2nd step of TH synthesis
2 DITs or 1 DIT and 1 MIT couple to form iodothyronines. The coupling reaction is thought to be catalyzed by thyroperoxidase as well
Half life of T3 & T4
T4: 7 days
T3: 1 day
What enzyme converts T4 to T3?
5’deiodinase (1& 2 are activating, 3 is inactivating)
T3 method of action
T3+receptor comples act on DNA to regulate transcription of different enzymes.
What conditions/drugs can inhibt 5’deiodinase
Neonatal period starvation severe illness stress drugs (GCs, propranolol, amiodrone, radiocontrast)
