Thyroid Hormones: Synthesis, Transport and Cellular Mechanisms Flashcards
What is the purpose of the thyroid hormones?
they maintain the level of metabolism in the tissues that is optimal for their normal funcitno
What are the formal names for T3 and T4?
- 3, 5, 3’ triiodothyronine = T3
- 3, 5, 3’,5’ tetraiodothyronine = T4
What cells synthesize the thyroid hormones?
synthesized by the follicular cells of the thyroid gland
Is T3 activity higher or lower than T4 activity?
•T3 activity > T4
What is Thyroglobulin?
•Thyroglobulin the precursor of T3 and T4
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•Large, iodinated protein: 2 subunits, each containing 115 tyrosine residues
Where is thyroglobulin synthesized?
synthesized in tyroid cells and secreted into colloid
How much T3 and T4 are stored in thyroglobulin?
•Thyroglobulin/colloid contains several weeks supply of T3/T4
What occurs when the thyroid hormones are required for secretion?
•
•When thyroid hormone secretion required:
–Colloid ingested by thyroid cells
–Peptide bonds hydrolysed
–T4/T3 released (and thyroglobulin)
How does iodine effect thyroid function?
•Iodine deficiency and excess can inhibit thyroid function
•
•150 microgrammes/day minimum intake
How is iodine taken up by the thyroid?
- Iodine actively transported from blood stream by iodide pump (ATP-ase dependent, NIS)
- Bound to tyrosine residues in colloid
- Iodide bound to the ‘3’ position of tyrosine molecules attached to thyroglobulin (Enzyme: thyroid peroxidase (TPO))
- MIT
- Bound to ‘5’ DIT
‘Coupling reaction’:
- MIT + DIT = T3
- DIT + DIT = T4
- (Enzyme: TPO)
What percent of the T4 and T3 are bound to plasma proteins?
T4= 99.98%
T3= 99.8%
- fail safe method that the body always has a store of T3 and T4 if the body needs it
What proteins bind T3 and T4 in circulation?
•TTR/TBPA, TBG (thyroid binding globulin), albumin
What sort of factors increase the amount of t3/T4 bound?
- TBG increased: oestrogen, pregnancy, clofibrate
- TBG decreased: Steroid therapy, androgen therapy
How do hormones effect the thyroid when they bind to the thyroid hormone receptors?
•Hormones enter cells and bind to thyroid hormone receptors in the nucleii
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•This complex binds to DNA and increases the expression of certain genes
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•Production of enzymes that alter cell function
Which thyroid hormone acts more rapidly? T3 or T4?
•T3 acts more rapidly than T4 and is 3 – 5 times more potent than T4
•
•T3 is less tightly bound to plasma proteins and more avidly bound to thyroid hormone receptors
•
How does the thyroid regulate hormone secretion?
TSH - a glycoprotein released from the anterior pituitary
2 subunits alpha and beta
What is the result of added TSH?
•Increased iodide binding
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•Increased number of microvilli on cells entrapping TG
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•Enhanced transcription of the TG gene
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•Increased coupling of MIT/DIT
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•Increased blood flow to the gland
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•Increased gland weight
Describe the negative feedback loop involved in the thyroid hormone secretion
•T4 and T3 inhibit TSH secretion and TSH synthesis (negative feedback)
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•TSH synthesis and secretion also regulated by TRH
- Normal FT4 10 – 23 pmol/L
- Normal TSH 0.4-5 mU/L
•
what is the diagnosis when patient has FT4 33 TSH <0.02 ??
high T4, but low TSH - due to negative feedback loop
*this is classic hyperthyroidism*
- Normal FT4 10 – 23 pmol/L
- Normal TSH 0.4-5 mU/L
What is diagnosis with patient •FT4 5 TSH 22 ??
Low FT4 and high TSH - hypothyroidism - the pituitary is trying to stimulate production of T4
- Normal FT4 10 – 23 pmol/L
- Normal TSH 0.4-5 mU/L
What’s the diagnosis with a patient…
FT4 6 TSH 2.3 ???
low FT4, but it’s not stimulating the pituitary to make more- therefore this could be a pituitary issue
