Thyroid Hormones: Synthesis and Regulation Flashcards
What is a goiter?
Enlarged thyroid
Does not describe the functional status of the gland
May be diffuse or nodular
What is the functional unit of the thyroid gland?
Follicle
A ductless alveolar structure surrounded by capillaries
What is thyroglobulin?
Glycoprotein where thyroid hormones are formed and stored
What are C cells?
Parafollicular cells located in the stroma surrounding the follicles
Produce Calcitonin
What are the secretory products of thyroid follicles?
Iodothryonines:
Thyroxine (T4)
Triiodothyronine (T3)
Reverse (rT3)
What is unique about thyroid hormones?
Only hormones to have iodine as a component
What is iodide trapping?
Transport system by which the thyroid gland absorbes iodine
Uses an Na/I symporter to move I against its concentration gradient
Efficiency is expressed in terms of the Thyroid/Serum Iodine ratio
What is the function of pendrin?
Iodide-chloride transporter responsible for transporting iodine into the follicular lumen for thyroid hormone formation
What is the function of thyroid peroxidase?
Oxidizes iodine as it enters the follicular lumen
Peroxide for this process is generated by thyroid oxidase
Also couples MIT and DIT to form T4 and T3
What occurs once iodine is oxidized?
Binds to tyrosyl residues in thryoglobulin forming monoiodotyrosine (MIT) and diiodotyrosine (DIT)
This process is called organification
What is coupled to form T4?
DIT + DIT
What is coupled to form T3?
MIT + DIT
What is the storage function of the MIT/DIT residues in thyroglobulin?
Serve as a reservoir for I
What is required for thyroid hormone release?
Proteolysis of thyroglobulin from the colloid via lysosomal proteases
T3 and T4 exit the basal surface
MIT and DIT remain in the cell and are deiodinated
What can occur in people deficient in microsomal iodotyrosine deiodinases?
Exhibit symptoms of hypothyroidism and have elevated urine MIT and DIT
What are the thyroid hormone binding proteins?
Thyroxine-Binding Globulin (TBG) - high binding affinity, T4>T3
Transthyretin - binds about 10% of T4, greater affinity for T4
Albumin -binds remainder
What conditions can affect circulating levels of TBG?
Levels decline in malnutrition, liver and kidney disease
Hepatic TBG synthesis stimulated by estrogen
Salicylates decrease thyroid hormone binding to TBG
What is the free fraction of thyroid hormones?
Hormone not bound to binding proteins
Available for tissue uptake
only about 0.03% of T4 and 0.3% of T3
What are the circulatory half lives of the thyroid hormones?
T4 - 6-7 days
T3 - one day
What are the major sources of T4 and T3?
All circulating T4 comes from the thyroid
Major sources of T3 are peripheral metabolism of T4 by the liver and kidneys
What is the function of iodothyronine deiodinases?
Peripheral deiodinases that catalyze the removal of specific iodine moieties
Maintain the circulating pool of T3
Local regulation allows specific target tissue to be independently regulated
Why can T4 be taken orally?
Sufficiently resistant to intestinal and hepatic degradation
What is the most important stimulator of thyroid gland growth and function?
Thyroid stimulating hormone (TSH) or thyrotropin
TSH secrtion is stimulated by thyrotropin releasing hormone (TRH)
Inhibited by T3 and T4
What is the pattern of secretion for TSH?
Pulsatile pattern and exhibits a circadian pattern
