Thyroid Hormone Synthesis Flashcards
location of thyroid gland
below larynx
thyroid structure
2 lobes in each side of trachea. A narrow band (isthmus) connects the 2 lobes
blood supply to thyroid
superior thyroid artery (from external carotid)and inferior thyroid artery (from thyrocervical trunk of subclavian)
T/F thyroid receives highest blood flow of all endocrine organs
True
functional unit of thyroid
follicle
follicle structure
layer of cells surrounding lumen filled with colloid. Colloid mostly made of thyroglobulin
types of cells in thyroid
follicular (surround colloid) and parafollicular cells (C cells)
role of parafollicular cells
parafollicular cells found between follicles and secrete calcitonin
ingredients for thyroid hormone synthesis
Iodide and tyrosine; Thyronine is the backbone of the THs, and the 3, 5, 3’, 5’ positions can be iodinated
thyroid hormones
Thyroxine (4 iodides) and triiodothyronine (3 iodides attached)
Iodide transport
ingest iodine from food– iodide absorbed from gut to enter blood/extracellular iodide pool– exits pool into follicular cells, difuses from basolateral to apical side and exits
where does organification of iodide occur
this occurs at follicular cell-colloid interface (must be oxidized before it can participate in tyrosyl iodination)
enzyme catalyzing iodination of thyroglobulin
thyroperoxidase; membrane bound glycoprotein in microvilli of apical membrane
Thyroglobulin
glycoprotein made on RER within follicular cells and transported to golgi for glycosylation and packaging. Secretory vesicles released from apical side to lumen where TG enters colloid
- all iodination and coupling reactions of TH synthesis occur on tyrosyl residues of TG
Thyroid hormone synthesis
thyroperoxidase catalyzes iodination of tyros)l moieties on TG to form monoiodotyrosine and diiodotyrosine (MIT and DIT) on TG. 2 DITs or 1 DIT and 1 MIT couple to form iodothyronines, thought to be catalyzed by thyroperoxidase
iodination inhibitors
inhibit iodination, causing decreased TH synthesis and secretion, which causes elevated TSH and gland hypertrophy (GOITER)
- thiourea drugs (propylhiouracil-PTU) and methimazole
- aka goiterogens
thyroid hormone secretion
Drops of colloid move into follicular cells via endocytosis and coalesce with lysosomes. Lysosomal enzymes cleave T4 and T3. Much more T4 than T4 (about 20x)
- DIT and MIT can also be cleaved, but these will be deiodinated and tyrosine/iodine reincorporated into TG
thyroid hormone transport
most protein bound (99.9%) and some in free form (.03% T4 and 0.3% T2)
- Free form is active
what proteins bind TH in blood
thyroid binding globulin (TBG), thyroid-binding pre-albumin (TBPA) and albumin
- about 30% of sites occupied by TH
role of protein bound TH
acts to delay, buffer, and prolong TH action; more pronounced for T4 than T3, partly since proportionally more T4 is bound due to higher affinity of TBG for T4