Case 9- thyroid hormones Flashcards
Hypothalamus- pituitary-thyroid (PHT) axis
In response to a stimulus, the hypothalamus releases thyrotropin-releasing hormone (TRH) which acts on the anterior pituitary. The anterior pituitary releases the thyroid stimulating hormone (TSH) into the blood. TSH then travels to the thyroid gland and stimulates production of thyroid hormones (T3 and T4)
Effects of TSH
↑ in size of follicular cells ↑ lysosomal activity ↑ pinocytosis of colloid ↑ iodination ↑ iodine uptake ↑ thyroglobulin synthesis
Thyroid hormone feedback
A type of negative feedback. An increase in T3 and T4 in the blood causes a reduction in TRH and TSH release
Hormones released- Hypothyroidism
↓ T3 & T4 but ↑ TSH
Hormones released- Hyperthyroidism
↑ T3 & T4 but ↓ TSH
Local control of Thyroid hormones
There is more T4 in the body but T3 is more active. Most plasma T3 is derived from the peripheral metabolism of T4. Conversion from T4 to T3 requires the removal of an iodine by a deiodinase enzyme. Thus, most T3 in the tissues is a result of tissue-specific type 2 deiodinase activity on T4. T4 can also be metabolised to reverse T3 which is inactive. By controlling the balance of T3 and rT3 tissues can manage their local thyroid status.
Receptor affinity for T3 and T4
All receptor types except TRa2 have a higher affinity for T3 than T4
Mechanism of action of T3 and T4
Circulating T3 and T4 require carrier mediated transport to cross the cell membrane. The 5’ deiodinase enzyme converts T4 to T3 in the cytoplasm. There are four thyroid hormone receptors-TR α1, α2, β1 and β2 (TRα2 does not bind T3). They exist as homodimers TR-TR or as heterodimers TR-RXR (retinol X receptor) bound to the thyroid response element (TRE) on the DNA. When T3 binds to the thyroid hormone receptor, gene transcription is activated to form mRNA followed by translation to a protein.
Proteins produced by T3
They are functional, involved in metabolism and structural, involved in growth
Metabolic function of the thyroid gland
1) Increase basic metabolic rate
2) Increases Glycolysis
3) Increases O2 consumption
4) Increases Thermogenesis
5) Increases protein turnover
Growth and development function of the thyroid gland
1) Fetal neural development
2) After birth it helps bone growth and tooth development
Neurological functions of the thyroid gland
1) Maintains emotional tone
2) Increases alertness, memory, reflexes and wakefulness
Cardiovascular function of the thyroid gland
1) Increase in cardiac output (HR and SV)
2) Increase in systolic pressure
3) Enhances catecholamine action via an increase in beta-adrenergic receptor activation
Reproductive function of the thyroid gland
1) Permissive role in males and female
Thyroxine (T4)
The most abundant hormone produced
Triiodothyronine (T3)
The most active thyroid hormone
Caticonin
Involved with calcium homeostasis in the blood in conjugation with the parathyroid gland
T3 and T4 synthesis- entering the cell
- TSH stimulates follicular cells to produce and excrete the protein Thyroglobulin into the colloid of the thyroid gland. Thyroglobulin contains Tyrosine
- Iodide is transported from the blood into the follicular cell through the sodium/iodide cotransporter.
- The iodide then moves into the colloid through the pendrin transporter.
T3 and T4 synthesis- Thyroid peroxidase
- Thyroid peroxidase is expressed on the apical membrane of follicular cells and oxidises iodide (negative) to Iodine.
- Thyroid peroxidase iodises thyroglobulin by attaching iodine tyrosine residues, when one is attached it creates MIT, when two are attached it creates DIT.
- Thyroid peroxidase also contributes to the coupling of the Tyrosine residues on Thyroglobulin. When DIT and MIT residues come together you get T3, when DIT and DIT residues come together you get T4.
T3 and T4 synthesis- follicular cell
- Thyroglobulin (containing the tyrosine residues) then enters the follicular cell and lysosomes fuse with the vesicle (containing Thyroglobulin) inside the cell releasing the enzymes. This then cleaves the Thyroglobulin into T3 and T4.
- There is then exocytosis of the thyroid hormones into capillaries where it binds with its transport proteins and moves around the body.
Free and bound thyroid hormones
The free hormone is active and the bound hormone acts as a reservoir. The increase or decrease in binding protein concentration changes the proportion of thyroid hormone that is free and biologically active. These proteins are produced by the liver and this process is stimulated by oestrogen and can therefore be affected by pregnancy and HRT.
What are thyroid hormones bound to?
0.1% of the thyroid hormones are free in the blood (unbound). The rest are bound to thyroid transport proteins: thyroid binding globulin (TBG) (70%), Albumin (20%) and transthyretin.
